Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Chehelgerdi, Matin; Behdarvand Dehkordi, Fereshteh; Chehelgerdi, Mohammad; Kabiri, Hamidreza; Salehian-Dehkordi, Hosein; Abdolvand, Mohammad; Salmanizadeh, Sharareh; Rashidi, Mohsen; Niazmand, Anoosha; Ahmadi, Saba; Feizbakhshan, Sara; Kabiri, Saber; Vatandoost, Nasimeh; Ranjbarnejad, Tayebeh

doi:10.1186/s12943-023-01873-0

Review
Open access
Published: 28 November 2023

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Matin Chehelgerdi^1,2,
Fereshteh Behdarvand Dehkordi^1,2,
Mohammad Chehelgerdi ORCID: orcid.org/0000-0002-3483-9424^1,2,
Hamidreza Kabiri^1,2,
Hosein Salehian-Dehkordi³,
Mohammad Abdolvand⁴,
Sharareh Salmanizadeh⁵,
Mohsen Rashidi^6,7,
Anoosha Niazmand⁴,
Saba Ahmadi⁸,
Sara Feizbakhshan⁴,
Saber Kabiri^1,2,
Nasimeh Vatandoost⁹ &
…
Tayebeh Ranjbarnejad⁴

Molecular Cancer volume 22, Article number: 189 (2023) Cite this article

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Abstract

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical and social implications, and the comparative analysis with other stem cell types for cancer treatment. The article will also discuss the applications of iPSCs in tumorigenesis, the future of iPSCs in tumorigenesis research, and highlight successful case studies utilizing iPSCs in tumorigenesis research. The conclusion will summarize the advancements made in iPSC-based tumorigenesis research and the importance of continued investment in iPSC research to unlock the full potential of these cells.

Introduction

Induced pluripotent stem cells (iPSCs) are a groundbreaking discovery in the field of stem cell research [1]. iPSCs are generated by reprogramming adult cells, such as skin cells or blood cells, back into a pluripotent state, similar to embryonic stem cells [2, 3]. This reprogramming is achieved by introducing a set of specific genes into the adult cells, which reactivates their dormant pluripotent capabilities [4, 5]. Once reprogrammed, iPSCs have the remarkable ability to differentiate into any type of cell in the body, including cells of the nervous system, heart, liver, and more [6,7,8,9] This versatility makes iPSCs a powerful tool in regenerative medicine, as they hold the potential to replace damaged or diseased tissues and organs [10]. In addition to their regenerative capabilities, iPSCs have also emerged as a valuable resource in cancer research. Cancer is a complex and multifaceted disease, characterized by the uncontrolled growth and proliferation of cells [11]. It is driven by genetic mutations and alterations in the epigenetic regulation of genes [12]. iPSCs offer a unique model for studying tumorigenesis, as they can be generated from adult cells that carry specific cancer-associated mutations. By studying these iPSCs, researchers can gain insights into the molecular changes that occur during the early stages of cancer development and progression. One of the key advantages of using iPSCs in cancer research is the ability to create disease-specific cell lines [13]. By reprogramming cells from cancer patients, iPSCs can be generated that carry the same genetic mutations found in the patient’s tumor cells. These iPSC-derived cells provide an invaluable tool for studying the molecular mechanisms underlying cancer development and progression [14]. Researchers can compare these iPSC-derived cancer cells with healthy iPSC-derived cells to identify the specific genetic and epigenetic changes associated with the disease. This knowledge can then be used to develop targeted therapies that specifically address the underlying molecular defects in individual patients [15]. Furthermore, iPSCs offer a platform for drug screening and testing in the context of cancer therapy. Traditional cancer drug development often relies on animal models or immortalized cancer cell lines, which may not accurately reflect the complexity of human cancer. iPSCs can be differentiated into various cell types that represent different stages of cancer development, allowing researchers to test the efficacy and toxicity of potential drugs in a more relevant cellular context. This personalized approach to drug screening holds great promise for improving the success rate of cancer treatments and reducing the side effects associated with conventional therapies [16]. The purpose of this review article is to provide a comprehensive overview of iPSCs in the context of tumorigenesis and therapy. We will discuss the current state of iPSC research, including the challenges and limitations associated with iPSC-based cancer therapy. Ethical and social implications of iPSC research will also be explored. Additionally, we will compare iPSCs with other types of stem cells, such as embryonic stem cells (ESCs) and adult stem cells, in terms of their potential for cancer treatment. We will delve into the various applications of iPSCs in tumorigenesis research, including their use in modeling cancer development, understanding molecular changes, and facilitating early detection of cancer. The review will also highlight successful case studies where iPSCs have been utilized to gain insights into tumorigenesis and develop novel therapeutic approaches. Ultimately, we aim to emphasize the importance of continued investment in iPSC research to fully unlock the promising potential of these cells in the field of cancer research and therapy.

The science behind iPSCs

Ghosh, Nehme, and Barrett emphasize the critical need for greater genetic diversity within human pluripotent stem cell models. Despite the expansion of repositories and studies in this field, a noticeable lack of genetic diversity persists. The authors underscore the significance of including diverse ancestral backgrounds in these models, highlighting that such inclusion is essential not only for promoting equity but also for expediting advancements in biological research and discovery [17]. The study, depicted in Fig. 1, analyzed the current landscape of genetic diversity in hPSC banks and human genomic studies. The findings revealed a significant underrepresentation of individuals with non-European and non-Asian ancestries in both repositories. This lack of diversity limits the generalizability of research findings and hinders our understanding of the impact of genetic variation on disease and treatment outcomes. The study emphasizes the importance of incorporating iPSCs into research initiatives, as illustrated in Fig. 1. By collecting material for iPSC reprogramming alongside genomic and phenotypic data, a direct link between genetic information and cellular resources can be established. This approach ensures that the genetic diversity of hPSC models is enhanced, enabling more accurate disease modeling and personalized medicine approaches. The iPSCs have emerged as a groundbreaking technology in the field of stem cell research [18] are generated by reprogramming adult somatic cells, such as skin cells or blood cells, into a pluripotent state similar to ESCs [19]. This reprogramming is achieved by introducing a set of defined transcription factors, known as the Yamanaka factors, into the adult cells. The Yamanaka factors include Oct3/4, Sox2, Klf4, and c-Myc, which are capable of reprogramming the cells’ gene expression patterns, allowing them to regain pluripotency [20]. The first generation of iPSCs emerged when Dr. Shinya Yamanaka and his team introduced the groundbreaking 4-factor protocol. This protocol involved the introduction of four key transcription factors—Oct4, Sox2, Klf4, and c-Myc—into somatic cells, effectively reprogramming them into iPSCs. Yamanaka’s discovery represented a pivotal moment in regenerative medicine, as it provided a relatively simple and reproducible method for generating iPSCs. These cells possessed the ability to differentiate into various cell types, making them invaluable for disease modeling, drug screening, and potential therapeutic applications [20]. Subsequent generations of iPSC reprogramming protocols aimed to improve safety and efficiency. The second generation involved the replacement of c-Myc, a potentially oncogenic factor, with alternative genes, such as Nanog or Lin28. This modification reduced the risk of tumorigenicity associated with c-Myc. Third-generation protocols focused on enhancing the efficiency of reprogramming, often incorporating small molecules and microRNAs to accelerate the process and improve the quality of iPSCs generated. These advancements brought iPSC technology closer to clinical applications by minimizing genetic abnormalities and increasing the yield of pluripotent cells [18]. The Yamanaka 4-factor protocol stands as a landmark achievement that laid the foundation for iPSC research, enabling scientists to harness the potential of these cells for various biomedical applications. As iPSC technology continues to evolve, it holds immense promise for personalized medicine, disease modeling, and regenerative therapies, offering hope for a future where patient-specific treatments are commonplace [19]. In a recent study, some researchers provided a groundbreaking approach to reprogram human somatic cells into chemically induced pluripotent stem cells (CiPSCs) was presented [21]. The study aimed to address the safety concerns associated with traditional methods of reprogramming, such as the use of viral vectors or ectopic expression of potential oncogenes. The researchers developed a fully defined and precisely staged chemically induced reprogramming protocol using small molecules. Lange et al. illustrates the process of chemically induced reprogramming, highlighting the key steps involved in transforming human somatic cells into human CiPSCs (Fig. 2). This method offers a potential solution to the challenges faced in clinical translation of iPSCs and opens up new possibilities for regenerative medicine. By generating pluripotent cells through a chemically induced approach, researchers can overcome ethical concerns and create personalized therapies for a wide range of diseases and conditions. The ability to generate iPSCs has revolutionized the field of regenerative medicine and opened up new possibilities for disease modeling, drug discovery, and personalized medicine [22]. iPSCs have the remarkable potential to differentiate into any cell type in the human body, making them an invaluable tool for studying human development, disease mechanisms, and therapeutic interventions [23]. One of the most significant advantages of iPSCs is their capacity to serve as a model for tumorigenesis [24]. Cancer is a complex disease characterized by the accumulation of genetic and epigenetic alterations that disrupt normal cellular processes. iPSCs can be reprogrammed from patient-derived cancer cells, allowing researchers to investigate the molecular changes and genetic abnormalities associated with cancer development [14]. By studying iPSCs derived from cancer patients, scientists can gain insights into the early events that initiate cancer and the subsequent processes that drive its progression [11]. Additionally, iPSCs offer a platform for drug screening and the development of personalized cancer therapies [25]. Patient-specific iPSCs can be differentiated into various cell types, including cancer cells, which can be used to test the efficacy and toxicity of different drugs [14]. This approach allows for the identification of personalized treatment options based on the specific genetic and molecular characteristics of an individual’s cancer [26]. By tailoring therapies to a patient’s unique genomic profile, iPSC-based approaches hold great promise for improving treatment outcomes and minimizing adverse effects. Despite their tremendous potential, there are several challenges associated with iPSC-based cancer therapy [27]. One of the major concerns is the tumorigenic properties of iPSCs themselves. iPSCs have the capacity to form tumors called teratomas when injected into living organisms. Teratomas consist of a mixture of different cell types derived from the three germ layers, highlighting the pluripotent nature of iPSCs [28]. To overcome this obstacle, researchers are actively exploring methods to improve the differentiation efficiency of iPSCs, ensuring that they fully mature into the desired cell type before transplantation. Another challenge is the efficient and safe delivery of iPSC-derived therapeutic cells to the tumor site [29]. Effective targeting and integration of iPSC-derived cells into the tumor microenvironment are critical for successful treatment outcomes [29]. Additionally, the potential immunogenicity of iPSCs and the risk of immune rejection need to be carefully considered when developing iPSC-based cancer therapies [30]. Ethical and legal considerations also come into play when working with iPSCs. The generation of iPSCs involves the use of human embryos or the reprogramming of adult cells, which raises ethical concerns and regulatory issues [31]. It is important to ensure that iPSC research is conducted ethically, with proper informed consent and adherence to established guidelines [32]. Comparative analysis with other stem cell types is crucial for evaluating the potential of iPSCs in cancer treatment (Table 1). While ESCs are considered the gold standard for pluripotent stem cells, their use is limited due to ethical concerns and immune rejection risks [33]. Adult stem cells, such as mesenchymal stem cells (MSCs), offer advantages in terms of immune compatibility but have limited differentiation potential [34]. iPSCs bridge this gap by providing a virtually unlimited source of patient-specific pluripotent stem cells with reduced immune rejection risks. In recent years, significant progress has been made in harnessing the potential of iPSCs for tumorigenesis research [22, 23]. Several successful case studies have demonstrated the utility of iPSCs in understanding the molecular mechanisms underlying cancer development and progression [35]. For instance, iPSCs derived from patients with specific types of cancer, such as leukemia or breast cancer, have been used to recapitulate the disease phenotype in a laboratory setting [15]. By studying these iPSC-derived cancer cells, researchers have gained valuable insights into the genetic and epigenetic alterations that contribute to tumor formation and progression. Moreover, iPSCs have been employed in cancer early detection strategies [36]. The ability to reprogram cancer cells into iPSCs allows for the identification of early molecular changes that occur during tumorigenesis [37]. By comparing iPSCs derived from healthy individuals with those derived from cancer patients, researchers can identify specific biomarkers or gene expression patterns that indicate the presence of cancer [38]. This knowledge could potentially revolutionize cancer diagnostics, enabling early detection and intervention when the disease is most treatable. In addition to cancer modeling and early detection, iPSCs hold promise in the development of precision medicine approaches for cancer treatment [36]. By generating iPSCs from patients with different types of cancer, researchers can create a diverse library of cancer cell lines that reflect the heterogeneity of the disease. Table 2 provides an overview of different iPSC lines. This resource can be used to test the effectiveness of various treatment options on individualized iPSC-derived cancer cells, allowing for the identification of targeted therapies tailored to a patient’s unique genetic profile. iPSC-based precision medicine has the potential to enhance treatment outcomes by improving the specificity and efficacy of cancer therapies while minimizing unnecessary side effects [26]. Looking ahead, the future of iPSCs in tumorigenesis research is filled with exciting possibilities. Advances in gene editing technologies, such as CRISPR-Cas9, combined with iPSCs, offer unprecedented opportunities for understanding the functional consequences of specific genetic alterations in cancer [39]. By precisely modifying the genome of iPSCs, researchers can investigate the effects of specific mutations or gene dysregulation on cancer development and progression. This knowledge can inform the development of targeted therapies that directly address the underlying genetic drivers of cancer [40]. Furthermore, ongoing efforts to improve the safety and efficiency of iPSC generation and differentiation techniques are crucial for their successful translation into clinical applications. Researchers are exploring novel reprogramming methods, such as the use of non-integrating viral vectors or small molecules, to enhance the efficiency and safety of iPSC generation [41]. Additionally, strategies to enhance the differentiation of iPSCs into specific cell types relevant to cancer therapy are being investigated, including the development of defined culture conditions and the use of signaling molecules or growth [29].

Table 1 Comparison of iPSCs with other stem cell types for cancer treatment

Full size table

Table 2 An overview of different types of iPSCs and their characteristics

Full size table

How iPSCs are derived

The iPSCs are derived through a groundbreaking technique that reprograms adult cells, enabling them to regain the pluripotent state similar to ESCs [73]. This discovery, made by Shinya Yamanaka in 2006, opened up new avenues in regenerative medicine, disease modeling, and drug discovery. Understanding how iPSCs are derived is essential to appreciate their potential and the implications for various fields of research and therapy [23]. The process of iPSC derivation involves the introduction of specific reprogramming factors into somatic cells, which are differentiated adult cells. These reprogramming factors can reset the cellular state, erasing the specialized characteristics of the somatic cells and reverting them back to a pluripotent state [74]. The most commonly used reprogramming factors are Oct4 (octamer-binding transcription factor 4), Sox2 (sex-determining region Y-box 2), Klf4 (Kruppel-like factor 4), and c-Myc (avian myelocytomatosis viral oncogene homolog) [20]. These factors work together to induce the expression of genes associated with pluripotency, while simultaneously repressing genes involved in cellular differentiation. The first step in iPSC derivation involves obtaining somatic cells from an individual [75]. These cells can be sourced from various tissues, including skin fibroblasts, blood cells, or even urine-derived cells. The choice of cell type depends on the research goals and the ease of accessibility [19]. Once the somatic cells are isolated, they are cultured in a laboratory setting and prepared for reprogramming. The reprogramming process typically involves the use of viral vectors or non-integrating methods to introduce the reprogramming factors into the somatic cells. Viral vectors, such as retroviruses or lentiviruses, have been widely used in the past. These vectors deliver the reprogramming factors into the somatic cells’ DNA, integrating the reprogramming genes into the host [76]. However, this method poses the risk of insertional mutagenesis and unwanted genetic changes. To address these concerns, researchers have developed non-integrating methods, such as the use of episomal plasmids, mRNA, proteins, or small molecules, which do not integrate into the host genome [77]. After the introduction of the reprogramming factors, the somatic cells undergo a transformation process. Over time, the cells gradually lose their original characteristics and acquire pluripotent features. The reprogramming factors initiate changes in gene expression patterns, leading to the reactivation of pluripotency-associated genes and the suppression of somatic cell-specific genes. This transformation can be visually observed, as the cells transition from a flat, adherent morphology to a distinct colony-like structure resembling ESCs [40]. The reprogramming process typically takes a few weeks, during which the cells are subjected to specific culture conditions to support their transition. These conditions often include the use of culture media supplemented with growth factors and small molecules that enhance the reprogramming efficiency [35]. The media composition and culture conditions vary depending on the specific protocols and the desired outcome of iPSC derivation. Once the iPSC colonies have formed, they are isolated and expanded for further characterization and experimentation. These iPSCs exhibit key characteristics of ESCs, such as self-renewal capacity and the ability to differentiate into cells of all three germ layers: ectoderm, endoderm, and mesoderm. iPSCs can be maintained in culture for prolonged periods, allowing for the generation of large quantities of cells for downstream applications [78]. The quality of derived iPSCs is crucial, as it affects their usability in various research and therapeutic applications. iPSCs must undergo rigorous characterization to ensure their pluripotent state and genomic integrity. Techniques such as immunostaining, gene expression analysis, and karyotyping are employed to confirm the expression of pluripotency markers and to assess the absence of genetic abnormalities or chromosomal aberrations. Immunostaining involves the use of specific antibodies to detect the presence of pluripotency markers, such as Oct4, Nanog, SSEA-4, and Tra-1–60, in iPSC [79]. Positive staining for these markers indicates that the cells have successfully acquired pluripotency and resemble ESCs. Additionally, gene expression analysis, such as reverse transcription-polymerase chain reaction (RT-PCR) or RNA sequencing, is performed to confirm the activation of pluripotency-associated genes and the silencing of somatic cell-specific genes [80]. Karyotyping, on the other hand, is a technique used to examine the chromosomal composition of iPSCs. It helps identify any chromosomal abnormalities or genetic mutations that may have occurred during the reprogramming process. This step is essential to ensure the genomic stability of iPSCs and to avoid potential issues related to aberrant chromosomal rearrangements [81]. After thorough characterization, the derived iPSCs can be used for a wide range of applications. They serve as a valuable tool for disease modeling, allowing researchers to study the underlying mechanisms of various diseases by generating patient-specific iPSCs. These iPSCs can be differentiated into specific cell types affected by the disease, providing a platform for understanding disease progression and developing personalized therapeutic strategies. Moreover, iPSCs hold great promise for drug discovery and screening [82]. In the field of regenerative medicine, iPSCs offer the potential for personalized cell-based therapies. By reprogramming a patient’s own somatic cells, iPSCs can be generated with the same genetic makeup as the individual, reducing the risk of immune rejection. These iPSCs can be differentiated into the desired cell types and used for transplantation, aiming to replace damaged or diseased tissues and organs [1, 7]. In a recent study conducted by Ezashi et al. (2009), the researchers successfully derived iPSCs from pig somatic cells, addressing the challenges associated with generating embryonic stem cells (ESCs) from ungulates [83]. Ezashi et al. employed lentiviral transduction of four human genes (hOCT4, hSOX2, hKLF4, and hc-MYC) commonly used for iPSC generation in mice and humans [83]. The iPSCs were derived from porcine fetal fibroblasts and cultured on irradiated mouse embryonic fibroblasts (MEFs) in a medium supplemented with knockout serum replacement and FGF2. Figure 3 of the study illustrates the process of generating piPSC colonies from plated fibroblasts (PFF), showcasing the successful reprogramming of porcine somatic cells. Furthermore, gene expression analysis conducted on the piPSCs is depicted in Fig. 3, confirming their pluripotent nature. Immunofluorescence staining results of piPSC colonies cultured on MEF can be seen in Fig. 3, providing visual evidence of their characteristics. Figure 3 compares the telomerase activity in different cell lines, demonstrating the high telomerase activity exhibited by the derived piPSCs, indicative of their cellular immortality. Moreover, the role of iPSCs in the study is particularly highlighted in Fig. 3, which shows the differentiation of pluripotent iPSCs into embryoid bodies (EB), representing the potential of these cells to give rise to various tissue types. Additionally, Fig. 3 presents a histological cross-section of a solid tumor surgically removed from the peritoneum of a hairless mouse, showcasing the in vivo potential and versatility of the piPSCs. Overall, this recent study successfully generated piPSCs from porcine somatic cells, shedding light on their potential applications in regenerative medicine, tissue engineering, and preclinical studies. The derivation of iPSCs involves the reprogramming of adult somatic cells to regain their pluripotent state. Through the introduction of specific reprogramming factors, somatic cells undergo a transformation process, losing their specialized characteristics and acquiring pluripotent features. The reprogramming process can be achieved using viral vectors or non-integrating methods [76]. The derived iPSCs must undergo rigorous characterization to confirm their pluripotency and genomic integrity. iPSCs hold immense potential in various fields, including disease modeling, drug discovery, and regenerative medicine, offering opportunities for personalized therapies and advancing our understanding of human development and disease [1, 7]. Continued research in iPSC technology will undoubtedly unveil further advancements and applications, paving the way for innovative approaches in biomedical research and clinical practice [23].

Characteristics of iPSCs and their potential in regenerative medicine

Characteristics of iPSCs

The iPSCs possess several key characteristics that make them highly valuable in regenerative medicine and disease research [1, 7]. The iPSCs possess several key characteristics that are highly relevant to the characterization of neural stem/progenitor cells (NS/PCs) derived from human iPSCs. Firstly, iPSCs share the defining feature of pluripotency, meaning they have the potential to differentiate into cells of all three germ layers, including neural cells [70]. This property allows for the generation of NS/PCs from iPSCs, serving as a valuable model system for studying neural development and disease. Secondly, iPSCs can be derived from adult somatic cells, such as skin cells, through reprogramming techniques, avoiding the ethical concerns associated with embryonic stem cells [1, 7]. This enables the generation of patient-specific iPSC lines, allowing for personalized medicine approaches and the study of neurological disorders using patient-derived cells. Additionally, iPSCs exhibit self-renewal capacity, allowing them to proliferate indefinitely in culture, thereby providing a sustainable source of NS/PCs for experimentation and potential therapeutic applications. Lastly, iPSCs can be genetically modified to introduce specific mutations or gene editing techniques, facilitating the investigation of genetic factors underlying neural development and diseases [70]. Isoda et al., the research focuses on understanding the tumorigenic potential of neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs), which are considered a promising source for cell-based therapies. The study establishes single cell-derived NS/PC clones (scNS/PCs) from hiPSC-NS/PCs that produced undesired grafts after transplantation. Through bioassays, the researchers identified unique subsets of scNS/PCs with a transcriptome signature resembling mesenchymal lineages. These scNS/PCs expressed both neural and mesenchymal markers and possessed osteogenic differentiation capacity. Significantly, removing CD73 + CD105 + cells from the parental hiPSC-NS/PC population was found to enhance the quality of hiPSC-NS/PCs and mitigate their tumorigenic potential. This research highlights the presence of unexpected cell populations within NS/PCs, shedding light on the tumorigenicity concerns associated with hiPSC-NS/PCs in the context of regenerative medicine [84]. Figure 4 provided a characterization of NS/PCs derived from hiPSCs, highlighting the importance of hiPSCs as a source for generating these neural cells. The study utilized a single cell-based approach, as depicted in Fig. 4, to analyze the variations within hiPSC-NS/PCs. This comprehensive analysis allowed the researchers to identify distinct subsets of scNS/PCs with a transcriptome signature indicative of mesenchymal lineages. Figure 4 demonstrated the presence of cells displaying mesodermal properties in grafts derived from hiPSC-NS/PCs, underscoring the importance of understanding the heterogeneity within the NS/PC population. Furthermore, Fig. 4 showcased the osteogenic differentiation capacity of NCC-like scNS/PCs, suggesting their potential to differentiate into bone-forming cells. To identify specific cell surface markers associated with osteogenic capacity, the researchers employed a strategy illustrated in Fig. 4. This allowed for the identification and purification of desired cell populations within hiPSC-NS/PCs, which is crucial for maintaining their quality and safety. Figure 4 presented a comparative analysis of the transcriptome signature of iPSC-NS/PCs, bona fide NCCs, and MSCs. This analysis shed light on the unique characteristics of iPSC-NS/PCs and their resemblance to both neural and mesenchymal lineages. Lastly, Fig. 4 demonstrated the process of purifying NS/PCs using CD15 as a marker to ensure the quality of the cell population. Overall, this recent study highlighted the mesenchymal properties observed in specific subsets of hiPSC-NS/PCs and their potential contribution to tumorigenicity. The findings emphasize the importance of understanding and characterizing the different cell populations within hiPSC-NS/PCs to enhance their safety and efficacy for future regenerative medicine applications. The study showcased the valuable role of iPSCs in generating NS/PCs and provided insights into their transcriptome signature, osteogenic differentiation capacity, and purification methods using specific cell surface markers.

Pluripotency

Pluripotency is a defining characteristic of iPSCs that has revolutionized the field of regenerative medicine. Pluripotent cells have the remarkable ability to differentiate into cells of all three germ layers: ectoderm, endoderm, and mesoderm. This unique property allows iPSCs to give rise to various cell types found in the human body, making them highly valuable for therapeutic applications, disease modeling, and tissue engineering [85]. In this article, we will explore the concept of pluripotency, its significance in iPSC research, and the potential it holds for advancing regenerative medicine. Pluripotency refers to the developmental potential of a cell to give rise to multiple cell lineages. It is characterized by the capacity to differentiate into cells of all three germ layers, which are the precursors of different tissues and organs in the body. Pluripotent cells are similar to the inner cell mass of the blastocyst, a stage of early embryonic development [85, 86]. In a recent study conducted by Bogliotti et al. (2023), the researchers focused on the efficient derivation of stable pluripotent bovine embryonic stem cells (bESCs) from bovine blastocysts. In a recent study conducted by Bogliotti et al. (2023), the primary focus was on achieving the efficient generation of robust pluripotent bovine embryonic stem cells (bESCs) from bovine blastocysts. The primary objective of their research was to tackle the challenge of establishing stable lines of bESCs, which hold great importance for a wide range of applications in genomics, genome engineering, and disease modeling. To optimize the derivation process, the research team employed a culture system that incorporated fibroblast growth factor 2 (FGF2) and an inhibitor of the Wnt-signaling pathway. Remarkably, they successfully produced pluripotent bESCs with consistent characteristics in terms of morphology, transcriptome, karyotype, population-doubling rate, expression of pluripotency marker genes, and epigenetic features. Notably, the study underscored the pivotal role of iPSCs within its context. Furthermore, the researchers emphasized the potential applications of the obtained bESCs, particularly in genomic selection, and the figures presented in the research yielded valuable insights [87]. Figure 5 illustrated the process and characterization of CTFR-bESCs, highlighting the significance of cystic fibrosis transmembrane conductance regulator (CTFR) in bESC derivation. Figure 5 depicted the distribution of histone methylation patterns in CTFR-bESCs, emphasizing the epigenetic features of these cells. Figure 5 presented molecular characteristics of CTFR-bESCs, shedding light on their genetic and transcriptional profiles. Finally, Fig. 5 showcased the various potential applications of CTFR-bESCs, specifically their role in genomic selection. Collectively, this recent study provides valuable insights into the efficient derivation of stable bESCs and highlights the significant role of iPSCs, as well as the potential applications of CTFR-bESCs in genomic selection. ESCs derived from the inner cell mass are naturally pluripotent. However, the groundbreaking discovery by Shinya Yamanaka in 2006 demonstrated that adult somatic cells can also be reprogrammed to a pluripotent state, resulting in the generation of iPSCs [88]. The induction of pluripotency involves reprogramming adult somatic cells back to an embryonic-like state. This process requires the introduction of specific transcription factors, known as the Yamanaka factors, into the somatic cells. These factors include Oct4, Sox2, Klf4, and c-Myc. The Yamanaka factors work together to activate pluripotency-associated genes and silence lineage-specific genes, effectively resetting the cell to a pluripotent state [89]. The discovery of iPSCs opened up new avenues for regenerative medicine, as it bypassed the ethical concerns associated with the use of human embryos and offered the potential for personalized cell therapies [7]. Pluripotency is a crucial characteristic of iPSCs that distinguishes them from other cell types. It provides researchers with an abundant and ethically sound source of pluripotent cells for various applications. iPSCs can be derived from patient-specific somatic cells, allowing for the generation of autologous pluripotent cells. This personalized approach overcomes the challenges of immune rejection often faced in transplantation therapies. Moreover, the pluripotent nature of iPSCs enables their differentiation into specific cell types relevant to regenerative medicine [1, 90]. Through controlled differentiation protocols, iPSCs can be directed to become cardiomyocytes, neurons, hepatocytes, or any other desired cell type. This ability opens up possibilities for tissue engineering, where iPSC-derived cells can be used to replace damaged or dysfunctional cells in various organs [23]. A recent study conducted by Eguchi et al. (2023) investigated the study delved into the impact of telomere shortening in cardiomyocytes affected by Duchenne muscular dystrophy (DMD). Furthermore, the research explored the feasibility of preserving telomeres as a potential therapeutic approach for addressing this condition [91]. The researchers utilized iPSCs derived from DMD patients to generate cardiomyocytes. In Fig. 6, the authors illustrated the differentiation process of iPSCs lacking the dystrophin gene into cardiomyocytes. The study compared DMD iPSC-derived cardiomyocytes (DMD iPSC-CMs) to control cells on day 30 of differentiation, as shown in Fig. 6. The DMD iPSC-CMs exhibited reduced cell size, nuclear size, and sarcomere density compared to the control cells. To address telomere attrition, the researchers focused on the telomeric repeat-binding factor 2 (TRF2), a key component of the shelterin complex. In Fig. 6, the study summarized the effects of TRF2 overexpression on preventing telomere attrition in DMD iPSC-CMs. The results showed that TRF2 expression rescued the deficiencies in cell size and sarcomere density. To assess telomere length, the researchers employed a bioengineered platform for calcium imaging and performed Southern blots of telomere restriction fragments. The study also investigated the impact of TRF2 on the DNA damage response and cell survival, as depicted in Fig. 6. The findings indicated that preventing telomere attrition through TRF2 overexpression ameliorated the activation of the DNA damage response and reduced premature cell death. Importantly, Fig. 6 demonstrated the effects of TRF2 on various cellular characteristics, including cell morphology, telomere length, activation of DNA damage response, and cell viability. Overall, these findings highlight the crucial role of iPSCs in studying disease mechanisms and therapeutic interventions, and suggest that preserving telomere length through TRF2 may hold promise for treating DMD-associated cardiac failure.

Self-renewal

Self-renewal is a fundamental property of stem cells that enables them to proliferate and maintain their undifferentiated state [15]. This property is critical for the regenerative potential of stem cells as it ensures a constant supply of cells for tissue repair and regeneration [38]. Self-renewal is a complex process that involves the regulation of multiple signaling pathways and gene networks. Understanding the mechanisms underlying self-renewal is essential for harnessing the therapeutic potential of stem cells. Self-renewal refers to the ability of stem cells to divide symmetrically or asymmetrically to produce daughter cells that retain their stem cell identity [92]. This process ensures a continuous supply of undifferentiated cells that can differentiate into specialized cell types. The balance between self-renewal and differentiation is tightly regulated to maintain tissue homeostasis and prevent the depletion of stem cell pools. Self-renewal is a fundamental characteristic of stem cells that underpins their regenerative potential [93]. The ability of stem cells to continuously proliferate while maintaining their undifferentiated state is crucial for tissue repair, transplantation, and disease modeling. The self-renewal capacity of stem cells, combined with their differentiation potential, makes them valuable tools for regenerative medicine, personalized therapies, and drug discovery [94]. Despite the challenges and complexities associated with self-renewal, ongoing research is steadily advancing our understanding of stem cell biology and paving the way for innovative applications in regenerative medicine. With further advancements in the field, the harnessing of self-renewal in stem cells holds great promise for revolutionizing healthcare and improving the treatment options available for a wide range of diseases and injuries [95].

Self-renewal in ESCs

ESCs are derived from the inner cell mass of blastocysts and are characterized by their pluripotency and unlimited self-renewal capacity. The self-renewal of ESCs is controlled by multiple signaling pathways, including the Wnt, FGF, and TGF-beta pathways, which interact with transcription factors such as Oct4, Sox2, and Nanog. These factors form a regulatory network that maintains the pluripotent state of ESCs and suppresses differentiation cues [96]. Adult stem cells, also known as somatic stem cells, are found in various tissues throughout the body and are responsible for tissue repair and regeneration. Adult stem cells have a more restricted differentiation potential than ESCs and are typically committed to a specific lineage. The self-renewal of adult stem cells is regulated by both intrinsic and extrinsic factors, including growth factors, cytokines, and niche microenvironments. One of the key intrinsic factors that regulate self-renewal in adult stem cells is the transcription factor Sox2 [97]. Sox2 is required for the maintenance of neural stem cells, hematopoietic stem cells, and mesenchymal stem cells. In addition, the Notch signaling pathway has been shown to play a critical role in the self-renewal of adult stem cells in various tissues, including the intestinal epithelium and the skin [19].

Challenges in self-renewal

While self-renewal is a critical property of stem cells, it can also lead to the accumulation of genetic and epigenetic changes that increase the risk of cancer and other diseases. The regulation of self-renewal is therefore a delicate balance that must be tightly controlled to prevent the over proliferation of stem cells. Another challenge in self-renewal is the loss of potency that can occur during long-term culture. As stem cells divide and differentiate, they may lose their ability to generate certain cell types or become more prone to differentiation into specific lineages. This loss of potency can limit the therapeutic potential of stem cells and must be addressed through rigorous quality control measures and optimization of culture conditions [25].

Applications of self-renewal in regenerative medicine

The self-renewal capacity of stem cells is critical for the development of regenerative therapies that aim to replace damaged or diseased tissues. By harnessing the regenerative potential of stem cells, researchers hope to develop new treatments for a wide range of diseases, including cardiovascular disease, diabetes, and neurodegenerative disorders. One of the most promising applications of self-renewal is in tissue engineering [19]. By combining stem cells with biomaterials and growth factors, researchers aim to generate functional tissues and organs that can be transplanted into patients. The ability of stem cells to self-renew ensures a sufficient supply of cells for tissue engineering, allowing for the creation of large-scale, complex tissues. For example, MSCs have shown promising self-renewal capacity and can differentiate into various cell types, making them valuable for engineering bone, cartilage, and other connective tissues [98]. In addition to tissue engineering, self-renewal plays a crucial role in the field of regenerative medicine by enabling the expansion of stem cell populations for therapeutic purposes. For instance, hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate into different blood cell types. HSC transplantation has been successfully used to treat various blood disorders, such as leukemia and aplastic anemia, where the self-renewal capacity of HSCs ensures a sustained production of healthy blood cells. The concept of self-renewal is also integral to the development of personalized medicine [99]. By isolating patient-specific stem cells and inducing their self-renewal, it is possible to generate a renewable source of cells for transplantation back into the same individual. This approach minimizes the risk of rejection and graft-versus-host disease, making autologous stem cell transplantation a promising option for personalized therapies. Furthermore, the self-renewal potential of stem cells holds significant implications for drug discovery and toxicology studies. Stem cells, including iPSCs, can be used to generate disease-specific or genetically modified cell lines that recapitulate the characteristics of certain diseases or specific patient populations [19]. This allows for the screening of potential drug candidates and evaluation of their efficacy and safety profiles, thereby facilitating the development of more targeted and personalized therapeutics [22].

Genetic stability

In the field of regenerative medicine, the genetic stability of iPSCs is a crucial aspect to consider. iPSCs, derived by reprogramming adult somatic cells, hold great promise for tissue engineering, disease modeling, and therapeutic applications. However, it is essential to ensure that the reprogramming process and subsequent culture conditions do not introduce genetic abnormalities or mutations that could compromise the safety and efficacy of iPSC-based therapies [1, 7]. This article explores the significance of genetic stability in iPSCs and the strategies employed to ensure the reliability of these cells for regenerative medicine purposes. Genetic stability refers to the preservation of the genetic information of iPSCs throughout the reprogramming process and subsequent cell culture. Any alterations or mutations in the genomic DNA of iPSCs can have profound implications for their clinical use. Genetic instability can lead to unintended consequences, such as aberrant differentiation potential, compromised functionality, or even the development of tumorigenic properties. Therefore, it is crucial to ensure the genetic integrity of iPSCs to maximize their potential in regenerative medicine [59].

Reprogramming methods

The choice of reprogramming methods can significantly influence the genetic stability of iPSCs. Various techniques, such as viral integration, non-integrating methods, and episomal vectors, have been used to deliver the reprogramming factors. Viral integration, although efficient, carries the risk of insertional mutagenesis. Non-integrating methods, such as mRNA or protein-based delivery, minimize the risk of genetic alterations. Researchers have focused on developing safer reprogramming approaches to enhance the genetic stability of iPSCs [100].

Quality control measures

Rigorous quality control measures are essential to assess the genetic stability of iPSCs. Whole-genome sequencing (WGS) and karyotyping are commonly employed techniques to analyze the entire genome and detect any chromosomal abnormalities or genetic mutations. WGS allows for the identification of single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and structural variations (SVs). Karyotyping, on the other hand, enables the examination of chromosome number and structure. These analyses help identify any genetic variations and ensure the genetic stability of iPSCs [101].

Epigenetic reprogramming

Epigenetic modifications play a vital role in cellular identity and function. During the reprogramming process, the epigenetic landscape of somatic cells is reset to an embryonic-like state. However, incomplete or aberrant epigenetic reprogramming can lead to genetic instability in iPSCs. Techniques such as DNA methylation profiling and histone modification analysis are used to assess the epigenetic status of iPSCs. Proper epigenetic reprogramming is crucial to maintain the genetic stability and pluripotency of iPSCs [102].

Long-term culturing conditions

Maintaining iPSCs in culture for extended periods can increase the risk of genetic instability. Factors such as culture media composition, substrate coating, and passaging methods can influence the genetic stability of iPSCs. It is important to optimize culture conditions to minimize the accumulation of genetic alterations over time. Researchers are continually exploring novel culture systems, such as feeder-free culture or defined media formulations, to enhance the genetic stability of iPSCs during long-term culturing [103].

Clonal expansion and characterization

Clonal expansion of iPSCs involves isolating and expanding individual iPSC colonies to ensure clonality and genetic homogeneity. This step helps identify and eliminate any genetically unstable iPSC lines. Furthermore, characterization of iPSCs at the molecular and functional level is essential to assess their genetic stability. Techniques such as immunocytochemistry, flow cytometry, and gene expression analysis can be employed to evaluate the pluripotency markers and differentiation potential of iPSCs. Additionally, functional assays can be performed to confirm their ability to differentiate into various cell lineages. Comprehensive characterization ensures that only genetically stable and functionally competent iPSC lines are selected for downstream applications [104].

Genome editing tools

Advances in genome editing technologies, such as CRISPR-Cas9, provide valuable tools to correct genetic abnormalities or introduce specific genetic modifications in iPSCs. This approach can be used to repair genetic mutations or eliminate unwanted genomic variations. Genome editing serves as a powerful strategy to enhance the genetic stability of iPSCs and ensure their suitability for regenerative medicine applications [105]. Recent studies have provided valuable insights into the epitranscriptomic control of pluripotent stem cell fate. In a groundbreaking investigation conducted the researchers delved into the influence of RNA modifications on the destiny determination of iPSCs [106]. Utilizing advanced high-throughput sequencing techniques, they discerned dynamic alterations in RNA modifications throughout the reprogramming process, where somatic cells were transformed into iPSCs. Their findings highlighted the critical importance of specific epitranscriptomic modifications, such as N6-methyladenosine (m6A) and N1-methyladenosine (m1A), in both acquiring and sustaining pluripotency. Furthermore, the researchers demonstrated that the manipulation of enzymes responsible for RNA modifications could enhance the efficiency of iPSC generation and steer the differentiation potential of iPSCs towards particular lineages. These results underscore the pivotal role of the epitranscriptome in governing iPSC fate and accentuate the potential utilization of epitranscriptomic modifications as targets for enhancing iPSC-based therapies. Additionally, Fig. 7 illustrates these findings, while Fig. 7 visually represents the diverse effects of various epitranscriptomic modifications on pluripotent stem cell characteristics, highlighting the intricate regulatory functions of RNA modifications in shaping the fate of pluripotent stem cells.

Immune compatibility

Regenerative medicine is a rapidly evolving field that aims to restore, replace, or regenerate damaged tissues and organs. One of the key challenges in this field is to develop therapeutic strategies that can avoid immune rejection and improve the long-term survival of transplanted cells and tissues. iPSCs have emerged as a promising tool in this regard, as they offer the potential to generate patient-specific cells that are immunologically compatible with the host [30]. While iPSCs offer great potential for immune compatibility in regenerative medicine, there are still challenges that need to be addressed. One major concern is the potential for immune rejection of iPSC-derived cells due to residual expression of immunogenic antigens or incomplete reprogramming. It is crucial to thoroughly characterize iPSC lines to ensure their safety and immunological compatibility before clinical application [25]. Another challenge is the long-term survival and functionality of iPSC-derived cells in the host environment. Even if immune rejection is minimized, the transplanted cells may still face challenges in integrating into the host tissue, establishing functional connections, and maintaining their desired phenotype [107]. Further research is needed to optimize differentiation protocols, enhance cell maturation, and improve the engraftment of iPSC-derived cells for successful long-term outcomes. Additionally, ethical considerations surrounding the use of iPSCs in regenerative medicine should not be overlooked. Issues such as the informed consent of donors, privacy of genetic information, and the potential for commercialization of iPSC-based therapies need to be carefully addressed to ensure responsible and ethical implementation [108].

Immune compatibility of iPSCs

The iPSCs possess several advantages over other sources of stem cells in terms of immune compatibility. Unlike ESCs, which are derived from embryos and may elicit an immune response when transplanted, iPSCs can be generated from adult somatic cells, such as skin fibroblasts or blood cells. This means that iPSCs can be produced from the same individual who will receive the therapy, minimizing the risk of immune rejection [25].

Autologous iPSCs

The use of autologous iPSCs, generated from a patient’s own cells, offers the greatest potential for immune compatibility. As the iPSCs are genetically identical to the donor, there is no risk of rejection or graft-versus-host disease. This approach is particularly useful in the treatment of diseases such as Parkinson’s disease, diabetes, or spinal cord injuries, where the goal is to replace lost or damaged cells with healthy ones. In these cases, iPSCs can be differentiated into the desired cell type, such as dopaminergic neurons or pancreatic beta cells, before transplantation. However, the generation of autologous iPSCs is not always feasible or practical. For example, patients with genetic disorders may have mutations present in all of their cells, making the generation of disease-free iPSCs difficult. Additionally, patients with advanced or widespread disease may not have a sufficient number of healthy cells to generate iPSCs. In these cases, allogeneic iPSCs, generated from a donor’s cells, may be utilized [109].

Allogeneic iPSCs

The use of allogeneic iPSCs raises the possibility of immune rejection, as the cells are genetically different from the host. However, several approaches are being explored to overcome this challenge. One approach is to use gene editing technologies, such as CRISPR/Cas9, to introduce genetic modifications into the iPSCs that reduce their immunogenicity. For example, researchers can delete or downregulate genes that code for major histocompatibility complex (MHC) molecules, which are responsible for presenting antigens to T cells and triggering an immune response. By reducing MHC expression, iPSCs may be able to evade detection by the host immune system. Another approach is to use immunosuppressive drugs, such as cyclosporine or tacrolimus, to dampen the host immune response. However, these drugs can have significant side effects and increase the risk of infection or malignancy. Therefore, alternative strategies that promote immune tolerance and reduce the need for immunosuppression are being investigated [110].

Promoting immune tolerance

One approach to promoting immune tolerance is to generate iPSC-derived cells that express immune-modulatory molecules, such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), or galectin-1. These molecules can inhibit T cell activation and promote the generation of regulatory T cells, which suppress immune responses. By incorporating these molecules into iPSC-derived cells, researchers aim to create a “tolerogenic” environment that can induce immune tolerance and reduce the risk of rejection [111].

Potential applications in regenerative medicine

The iPSCs can be differentiated into specific cell types relevant to tissue repair and regeneration. For instance, they can be directed to differentiate into cardiomyocytes for cardiac tissue regeneration, hepatocytes for liver tissue engineering, or neurons for the treatment of neurological disorders. The ability to generate patient-specific cells holds great promise for developing customized therapies and overcoming the limitations associated with organ transplantation. The iPSCs provide a valuable platform for studying the mechanisms underlying various diseases. By reprogramming cells from patients with genetic disorders or complex diseases, researchers can generate disease-specific iPSC lines that recapitulate the pathology in a controlled laboratory setting [19]. These disease models allow for a better understanding of disease progression, identification of novel therapeutic targets, and screening of potential drugs. Traditional drug development processes rely heavily on animal models and can be time-consuming and costly. iPSCs offer an alternative approach by providing human-specific cell models for drug screening and toxicity testing. iPSC-derived cells, such as cardiomyocytes or hepatocytes, can be utilized to evaluate the efficacy and safety of drug candidates, reducing the need for animal testing and improving the accuracy of preclinical studies. In certain degenerative diseases, such as Parkinson’s disease or diabetes, iPSCs hold the potential to replace damaged or dysfunctional cells [23]. By differentiating iPSCs into the desired cell type, such as dopaminergic neurons or pancreatic beta cells, researchers aim to restore lost function and alleviate disease symptoms. However, challenges related to the scalability, maturation, and long-term safety of iPSC- derived cells need to be addressed before widespread clinical application [7].

Advancements in the field of iPSC research

Over the past decade, the field of iPSC research has seen significant advancements and progress. iPSCs are a type of stem cell that are created by reprogramming adult cells to a pluripotent state, meaning they have the potential to develop into any type of cell in the body. This technology has opened up new avenues for regenerative medicine, disease modeling, drug discovery, and personalized medicine [1]. One of the most significant advancements in iPSC research has been the development of more efficient and reliable methods for reprogramming adult cells. Early methods of reprogramming involved the introduction of transcription factors into cells using viruses, which posed a risk of mutations and potential tumorigenesis. However, recent advances have utilized non-viral methods such as mRNA, microRNA, and small molecules, which are safer and more efficient [112]. These methods have also led to the production of high-quality iPSCs with improved differentiation potential and reduced genomic abnormalities. Another area of advancement in iPSC research is the development of more sophisticated techniques for manipulating and controlling iPSC differentiation. Scientists can now direct iPSCs to differentiate into specific cell types, such as neurons, cardiac cells, and pancreatic cells, using specific growth factors, signaling molecules, and genetic manipulation [19]. This has led to the creation of more complex in vitro models of human disease, allowing for the study of disease mechanisms and drug screening. In addition, iPSC research has made significant strides in the field of personalized medicine. iPSCs can be generated from a patient’s own cells and then differentiated into specific cell types, allowing for the creation of personalized disease models and drug screening platforms. This has the potential to revolutionize drug discovery, as it allows for the identification of patient-specific drug targets and the development of personalized treatment plans. Another major advancement in the field of iPSC research is the use of gene editing techniques such as CRISPR-Cas9 to manipulate the genome of iPSCs [7]. This has allowed for the creation of disease-specific iPSC lines with specific genetic mutations, which can be used to study disease mechanisms and test potential therapies. Gene editing also holds potential for the development of gene therapies, which could treat genetic diseases by correcting mutations in iPSCs and then differentiating them into the affected cell type. Advancements in iPSC research have also led to new approaches in cancer research and therapy [1]. iPSCs can be used to model cancer development and progression, allowing for the identification of genetic and epigenetic changes that drive tumor growth. Additionally, iPSCs can be used to develop personalized cancer treatments, such as chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy involves reprogramming a patient’s own T cells using iPSC technology, allowing them to specifically target and kill cancer cells [113]. Finally, advancements in iPSC research have raised important ethical and legal considerations. The creation and use of iPSCs raises questions about ownership, consent, and the potential for genetic manipulation and designer babies. Additionally, the use of iPSCs in drug screening and disease modeling could lead to the exploitation of vulnerable populations, such as those with rare genetic diseases [22].

iPSCs in cancer therapy

One of the key advantages of iPSCs in cancer therapy is their ability to serve as models for studying cancer biology [1]. By reprogramming somatic cells from cancer patients into iPSCs, researchers can generate patient-specific cell lines that retain the genetic and epigenetic characteristics of the original tumor [2]. These iPSC-derived cancer cells can be differentiated into different cell types and used to study the mechanisms of cancer development, progression, and response to treatment [3]. This approach provides a unique opportunity to investigate individualized responses to various therapies and develop personalized treatment strategies [4].

iPSCs as a source of cancer cells for research and drug screening

The iPSCs have demonstrated great potential as a valuable tool for studying cancer biology and developing novel therapies [2]. One significant application of iPSCs in cancer research is their use as a source of cancer cells for in vitro studies and drug screening [4]. By reprogramming somatic cells from cancer patients, researchers can generate iPSC lines that harbor the genetic and epigenetic alterations characteristic of the individual’s cancer [1]. These patient-specific iPSCs can be further differentiated into various cancer cell types, allowing for the creation of in vitro models that closely resemble the patient’s tumor [1]. This enables researchers to study the molecular mechanisms underlying cancer initiation, progression, and response to treatment. By comparing iPSC-derived cancer cells with healthy cells from the same individual, scientists can identify key genetic and epigenetic changes that contribute to cancer development [5]. Moreover, iPSC-derived cancer cells provide a platform for drug screening and testing. Researchers can expose these cells to different therapeutic agents to evaluate their efficacy and selectivity against the specific cancer type [5]. iPSC-derived models allow for personalized medicine approaches, where drugs can be screened on patient-specific cancer cells to identify the most effective treatment options [6]. This personalized approach has the potential to revolutionize cancer therapy by tailoring treatments to individual patients, improving treatment outcomes, and reducing adverse effects [7]. Table 3 provides an overview of the utilization of iPSCs as a valuable source of cancer cells for research and drug screening purposes.

Table 3 iPSCs as a source of cancer cells for research and drug screening

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Personalized cancer treatment using iPSCs

The ability to generate patient-specific iPSCs opens up new possibilities for personalized cancer treatment [2]. Traditional cancer treatments, such as chemotherapy and radiation therapy, often lack specificity and can have significant side effects. iPSCs offer a unique opportunity to develop personalized therapies that target cancer cells while sparing healthy tissues [5]. By reprogramming somatic cells from patients into iPSCs, researchers can differentiate these iPSCs into various cell types, including immune cells [6]. iPSC-derived immune cells can be genetically modified to enhance their tumor-targeting capabilities, such as expressing chimeric antigen receptors (CARs) or T-cell receptors (TCRs) specific to cancer antigens [8]. These modified immune cells, also known as iPSC-derived CAR-T or TCR-T cells, can be expanded in large quantities and reinfused into the patient [2]. As these cells are derived from the patient’s own cells, the risk of immune rejection is minimized. Personalized cancer immunotherapies using iPSC-derived immune cells have shown promising results in preclinical studies [8]. They hold the potential to improve the efficacy and specificity of cancer treatment while reducing off-target effects. However, challenges such as ensuring the safety and effectiveness of iPSC-derived immune cells, optimizing their differentiation protocols, and overcoming immune evasion mechanisms employed by cancer cells need to be addressed before their widespread clinical application [9]. Table 4 provides an overview of the potential of personalized cancer treatment through the use of iPSCs.

Table 4 An overview of personalized cancer treatment utilizing iPSCs

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iPSCs for developing immunotherapies for cancer

Immunotherapies have emerged as a breakthrough approach in cancer treatment, harnessing the power of the immune system to selectively target and eliminate cancer cells. iPSCs offer unique advantages for developing immunotherapies by providing an unlimited source of immune cells for manipulation and expansion [8]. One promising strategy is the generation of iPSC-derived dendritic cells (DCs). DCs play a crucial role in initiating and regulating immune responses. iPSC-derived DCs can be engineered to express specific tumor antigens or antigen-presenting molecules, enhancing their ability to activate immune cells against cancer cells [10]. These iPSC-derived DCs can be used as vaccines to stimulate an anti-tumor immune response in patients. Additionally, iPSCs can be differentiated into natural killer (NK) cells, a type of immune cell known for their ability to recognize and kill cancer cells. iPSC-derived NK cells can be genetically engineered to enhance their tumor-targeting capabilities and to improve their persistence and cytotoxicity [11]. These modified iPSC-derived NK cells can then be used as a potent immunotherapy for cancer treatment [12]. Furthermore, iPSCs can be utilized to generate tumor-specific T cells. Tumor-infiltrating lymphocytes (TILs) obtained from cancer patients have shown promising results in immunotherapy. However, their limited supply and functional exhaustion pose challenges for clinical applications [13]. iPSCs provide a renewable source for generating TILs in large quantities. iPSC-derived T cells can be genetically modified to express tumor-specific TCRs or CARs, enabling them to recognize and eliminate cancer cells [14]. These iPSC-derived T cells can be expanded and infused back into the patient to mount an effective anti-tumor immune response [15]. The use of iPSCs for developing immunotherapies offers the potential for personalized treatments and improved clinical outcomes [15]. By combining the advantages of iPSC technology with the specificity and potency of immune cells, researchers are paving the way for more targeted and effective cancer therapies. Table 5 highlights the utilization of iPSCs in the advancement of immunotherapies for cancer.

Table 5 iPSCs for developing immunotherapies for cancer

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Mechanisms of iPSC-based cancer therapy

The iPSCs have shown tremendous potential in the field of cancer therapy. Their unique characteristics, such as pluripotency and self-renewal, enable the development of innovative approaches for the treatment of various types of cancer [473].

iPSC-derived cancer cells for drug screening and personalized treatment

One of the major challenges in cancer treatment is identifying effective drugs that specifically target cancer cells while sparing healthy cell [474]. iPSCs offer a valuable tool for addressing this challenge by providing a platform for generating patient-specific cancer cells [475]. By reprogramming somatic cells from cancer patients into iPSCs, it is possible to differentiate them back into cancer cells representing the patient’s specific tumor type [15]. These iPSC-derived cancer cells can be used for drug screening and testing the efficacy of various anticancer drugs [105]. Researchers can expose these cells to different compounds and observe their response, allowing for the identification of personalized treatment options. This approach has the potential to improve the success rate of cancer treatment by tailoring therapies to individual patients based on the characteristics of their specific cancer cells [476]. In a recent investigation carried out by Ware et al. (2014), the primary focus was on obtaining nontransgenic hESCs in a naïve state and examining their properties and potential for development [477]. This study builds upon prior research that had demonstrated the advantages of achieving a naïve pluripotent state in mice while highlighting the challenges in replicating the same state in human cells. The researchers employed two strategies for obtaining naïve hESCs. Firstly, they successfully converted existing primed hESC lines into the naïve state by exposing them to histone deacetylase inhibitors, followed by cultivation with MEK/ERK and GSK3 inhibitors (2i) along with FGF2. Secondly, they directly derived naïve hESCs from human embryos using 2i and FGF2. The resultant naïve hESCs exhibited traits consistent with the naïve state, including growth patterns, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile, and developmental potential in teratomas. Importantly, this research also underscores the role of iPSCs in the context of naïve hESCs. iPSCs are somatic cells reprogrammed to a pluripotent state akin to embryonic stem cells. In Fig. 8, the researchers illustrate the influence of 2i culture on both mouse and human pluripotent cells, emphasizing the adaptability of these culture conditions to various pluripotent cell types, including iPSCs. Furthermore, Fig. 8 presents diverse genomic analyses conducted on naïve hESCs, shedding light on the molecular attributes of these cells and their comparison to other pluripotent states, including iPSCs. Additionally, Fig. 8 offers a comprehensive analysis of the stages of pluripotency in hESCs using various techniques, providing insights into the distinct characteristics of naïve hESCs and their relationship with iPSCs. Lastly, Fig. 8 illustrates the developmental potential of teratomas derived from different cell states, encompassing naïve and primed hESCs. This underscores the importance of comprehending and characterizing pluripotent states, including naïve and iPSCs, due to their significant implications for research in regenerative medicine and developmental biology.

iPSCs for developing cancer vaccines and immunotherapies

Immunotherapy has emerged as a promising approach for cancer treatment, harnessing the body’s immune system to target and eliminate cancer cells. iPSCs offer a novel avenue for developing cancer vaccines and immunotherapies [478]. Researchers can reprogram iPSCs to express specific tumor antigens, which are proteins found on the surface of cancer cells that can trigger an immune response [479]. These iPSCs can be differentiated into dendritic cells or other antigen-presenting cells, which are crucial for activating the immune system [480]. The iPSC-derived antigen-presenting cells can then be used to stimulate the patient’s immune system, priming it to recognize and attack cancer cells expressing the specific tumor antigens. This approach holds promise for the development of personalized immunotherapies that target the unique characteristics of each patient’s cancer cells [481]. Table 6 highlights the significant role of iPSCs in the field of cancer vaccines and immunotherapies.

Table 6 iPSCs for developing cancer vaccines and immunotherapies

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Utilizing iPSCs for cancer cell differentiation and apoptosis

Another mechanism through which iPSCs contribute to cancer therapy is by directing their differentiation into specific cell types that can target and eliminate cancer cells [25]. Researchers can guide iPSCs to differentiate into immune cells, such as NK cells or T cells, which have the ability to recognize and destroy cancer cells [25]. The iPSC-derived NK cells can be engineered to enhance their anti-cancer properties, such as increasing their cytotoxic activity or improving their targeting capabilities. These modified iPSC-derived NK cells can then be used as a cell-based therapy to directly kill cancer cells figure [131]. Similarly, iPSC-derived T cells can be modified to express CARs that recognize specific cancer cell antigens, enabling them to selectively target and eliminate cancer cells [488]. Furthermore, iPSCs can be used to induce apoptosis, programmed cell death, in cancer cells. By understanding the signaling pathways and molecular changes that drive cancer cell survival, researchers can engineer iPSCs to produce and release therapeutic molecules or microRNAs that promote cancer cell apoptosis [481]. This approach offers a potential strategy for selectively eliminating cancer cells while minimizing harm to healthy cells.

Current limitations and challenges in iPSC-based cancer therapy

In recent years, iPSCs have emerged as a promising tool in the field of cancer therapy. These cells, which can be derived from adult somatic cells and reprogrammed to exhibit pluripotency, hold great potential for personalized medicine and regenerative therapies [489]. However, despite the significant progress made in this area, there are several limitations and challenges that need to be addressed before iPSC-based cancer therapy can be widely adopted. One of the major challenges in iPSC-based cancer therapy is the technical difficulty associated with generating high-quality iPSCs [490]. The reprogramming process itself is complex and inefficient, often resulting in low-quality iPSCs with genomic abnormalities [491]. These abnormalities can limit the therapeutic potential of iPSCs and may even pose safety risks, such as tumorigenicity [491]. Researchers are actively working on improving the efficiency and quality of iPSC generation. Techniques such as the use of non-integrating reprogramming methods, optimization of culture conditions, and the development of novel reprogramming factors are being explored to enhance the generation of high-quality iPSCs [492, 493]. However, further research is needed to overcome these technical difficulties and ensure the reliable production of iPSCs for cancer therapy. Another significant challenge in iPSC-based cancer therapy lies in the regulatory and safety aspects of using these cells in clinical settings [494]. iPSCs, being a relatively new technology, pose unique regulatory challenges. The regulatory agencies need to establish clear guidelines and standards for the production, characterization, and quality control of iPSCs for cancer treatment [40]. Safety is also a crucial concern when using iPSCs in cancer therapy. As mentioned earlier, iPSCs can harbor genomic abnormalities that could potentially lead to tumorigenicity. Rigorous safety assessments and monitoring protocols should be implemented to minimize the risk of adverse events and ensure patient safety [495]. The use of iPSCs in cancer therapy raises important ethical and legal concerns that need to be carefully addressed [496]. The generation and manipulation of iPSCs involve the use of human embryos or adult somatic cells, which raises ethical questions regarding the source of cells and the potential destruction of embryos [497]. To navigate these ethical challenges, researchers and policymakers must engage in comprehensive discussions and establish clear guidelines regarding the sources of cells, informed consent, and the potential uses of iPSCs in cancer therapy [497]. Striking a balance between scientific advancement and ethical considerations is crucial to ensure the responsible and ethical use of iPSCs in cancer treatment. In addition to the ethical concerns related to the source of cells, there are broader ethical and legal concerns surrounding the use of iPSCs in cancer therapy. These concerns include issues of privacy, consent, and potential commercial exploitation of iPSC technology [498]. The use of iPSCs for personalized cancer therapy requires the collection and storage of patients’ biological materials, including somatic cells. Ensuring the privacy and confidentiality of patients’ data is essential to maintain trust in the healthcare system. Moreover, there is a need to address potential conflicts of interest and ensure equitable access to iPSC-based cancer therapies. Policies and regulations should be in place to prevent the commercial exploitation of iPSC technology and to promote fair and affordable access to these treatments. Generating high-quality iPSCs remains a technical challenge in iPSC-based cancer therapy [499]. The reprogramming process can be affected by various factors, such as the age and quality of the somatic cells used as the starting material [500]. Researchers have observed that iPSCs derived from older donors or from cells with genetic abnormalities tend to have a higher risk of genomic instability and lower differentiation potential [501]. Overcoming these technical difficulties is crucial to ensure the generation of iPSCs that are suitable for use in cancer therapy. Efforts are underway to improve the efficiency and reliability of iPSC generation. Researchers are exploring different reprogramming methods, including the use of small molecules and modified RNA, to enhance the efficiency and quality of iPSC production [502, 503]. Additionally, advancements in gene editing technologies such as CRISPR-Cas9 are being utilized to correct genomic abnormalities in iPSCs, further improving their quality and safety [504]. Regulatory and safety issues are significant challenges that need to be addressed when considering the use of iPSCs in cancer treatment. The regulatory landscape for iPSC-based therapies is still evolving, and regulatory agencies are actively working to establish guidelines and standards [505]. Safety concerns related to iPSC-based cancer therapy include the potential for tumor formation and immune rejection [506, 507]. To mitigate these risks, extensive preclinical studies and rigorous safety assessments are required before iPSC-based therapies can progress to clinical trials [508]. Long-term monitoring and follow-up of patients receiving iPSC-based treatments are also necessary to evaluate their safety and efficacy [507]. Moreover, regulatory agencies need to establish clear criteria for the characterization and quality control of iPSCs used in cancer therapy [509]. This includes ensuring that the iPSCs have the desired pluripotent properties and are free from genetic abnormalities and contaminants [510]. While iPSC-based cancer therapy holds immense promise, there are several limitations and challenges that need to be overcome. Technical difficulties in generating high-quality iPSCs and addressing regulatory, safety, ethical, and legal concerns are crucial areas that require further research and development [511]. Collaboration among researchers, policymakers, and regulatory agencies is essential to navigate these challenges and unlock the full potential of iPSC-based cancer therapy, ultimately leading to improved patient outcomes and personalized treatments in the future.

The biogenesis of cancer

Cancer is a multistep disease that is characterized by continuous and excessive cell division. Globally, it is the second leading cause of death [16, 17]. Cancer is caused by genetic mutations and epigenetic alterations. During the initial stages of cancer development, normal cells undergo transformation toward a neoplastic state, acquiring new capabilities such as unlimited replicative potential, resistance to cell death, and stimulation of angiogenesis. Biogenesis refers to the process by which normal cells become cancerous [18]. This article will explore the various aspects of tumorigenesis, including the cancer cell-of-origin hypothesis, the interplay between genetics, epigenetics, and environmental factors, and the role of stem cells in tumorigenesis.

Overview of tumorigenesis

During the past 20 years, we have gained a great deal of knowledge about how various cancers develop at the molecular and cellular levels [19]. Variability in response to anti-cancer drugs among cancer patients can be elucidated by genetic molecular features such as mutations and copy number changes, and DNA methylation [20]. In addition to improving our understanding of this process, identifying genes and pathways involved will also help us to develop new therapeutic targets [21]. In cancer, chromosomal changes and genes are disrupted through genomic approaches. It is recognized that tumorigenesis is a complex process that involves progressive transformations triggered by multiple factors and it is regulated by both oncogenes and tumor suppressor genes. Several growth-promoting and growth-restricting mechanisms regulate the cell cycle which is crucial for proper division and propagation. A disruption of this regulation may lead to uncontrolled proliferation and genomic instability, which may trigger the development of cancer [22]. Activation of oncogenes leads to tumorigenesis, which controls cell proliferation and apoptosis. They can be activated by structural alterations resulting from mutation or gene fusion. Additionally, tumor suppressor genes (TSG) encode proteins that regulate cell proliferation negatively. They have included in two classes: the “caretakers” of the genome (or Type I), which are DNA repair genes that protect the genome from mutations (XPB, MSH2, etc.), and the gatekeepers (or Type II), which avert cancer through direct control of cell growth (p53, p16, etc.).The inactivation of tumor suppressor genes by loss or mutation is a vital step for the development of tumors [23]. Besides genetic alterations, epigenetic mechanisms contribute to the development of malignant phenotypes, according to growing evidence [24]. The study of epigenetics, which is dynamic and susceptible to environmental factors, is concerned with mechanisms that change gene expression without altering the primary DNA sequence. Epigenetic processes are heritable and reversible and consist of changes in DNA methylation, histone modifications, small noncoding microRNAs (miRNA), and nucleosome remodeling [25]. The alteration of cellular methylation status by a specific methyltransferase might explain the differences in the probability of malignant transformation [26]. Tumor cells in different tissue with a wide range of patterns of histone modification, genome-wide or in individual genes, demonstrate the presence of epigenetic heterogeneity at a cellular level [27]. The combined action of multiple epigenetic factors results in tumorigenesis. For example, the repression of tumor suppressor genes is caused by the methylation of DNA CpG islands with hypoacetylated and hypermethylated histones [28]. Several hallmarks of epigenetic events have been identified during gene silencing, including histone H3 and H4 hypoacetylation, histone H3K9 methylation, and cytosine methylation [29].

Overview of the cancer cell-of-origin hypothesis

The cancer cell-of-origin hypothesis is a fundamental concept in cancer research that aims to identify the specific type of cell from which a tumor originates [512]. This hypothesis suggests that certain cancers arise from a small subset of cells within a tissue or organ that possess unique properties, enabling them to acquire the genetic and epigenetic alterations necessary for tumor initiation and progression [513]. According to recent studies published in renowned scientific journals, researchers have made significant progress in elucidating the origins of various types of cancer [512]. Some studies focused on breast cancer, revealing that a small population of mammary stem cells, which normally aid in the maintenance and repair of breast tissue, can undergo genetic mutations that transform them into cancer-initiating cells. These findings support the cancer cell-of-origin hypothesis, highlighting the importance of targeting these specific cells for effective treatment strategies [514]. Another study investigated the origins of brain tumors, specifically glioblastoma, one of the most aggressive and lethal forms of brain cancer [515]. By analyzing human brain tissue samples and using advanced genetic sequencing techniques, scientists identified a subset of neural stem cells as the likely cell-of-origin for glioblastoma. These cells possess the ability to self-renew and differentiate into various types of brain cells, making them susceptible to acquiring oncogenic mutations that lead to tumor formation [514]. In addition to breast and brain cancer, the cancer cell-of-origin hypothesis has also been explored in other malignancies [516]. Research on colorectal cancer has suggested that a small population of intestinal stem cells may give rise to the development of adenomas, the precursor lesions of colorectal cancer [517]. Similarly, in skin cancer, studies have implicated epidermal stem cells as the cell-of-origin for various types of skin tumors, including basal cell carcinoma and squamous cell carcinoma [518]. Understanding the cell-of-origin for different cancers is not only crucial for unraveling the molecular mechanisms underlying tumor development but also has significant implications for personalized medicine and targeted therapies [519]. By identifying and characterizing the unique properties of cancer-initiating cells, researchers can develop strategies to specifically target and eliminate these cells, thus preventing tumor recurrence and improving patient outcomes [518]. Advancements in single-cell sequencing technologies have played a pivotal role in advancing our understanding of the cancer cell-of-origin hypothesis. These cutting-edge techniques enable researchers to analyze individual cells within a tumor and decipher their genomic and epigenomic landscapes [520]. By comparing the genetic profiles of cancer-initiating cells with their normal counterparts, scientists can identify key genetic alterations that drive tumor initiation and progression [521]. Moreover, the cancer cell-of-origin hypothesis has prompted further investigation into the role of the tumor microenvironment in tumor development [521]. Emerging evidence suggests that interactions between cancer-initiating cells and their surrounding microenvironment, including immune cells, fibroblasts, and blood vessels, play a critical role in promoting tumor growth and metastasis [522]. Targeting these interactions may provide novel therapeutic opportunities for cancer treatment. The cancer cell-of-origin hypothesis has revolutionized our understanding of tumor initiation and progression [523]. By identifying the specific cells from which cancers originate, researchers have made significant strides in deciphering the underlying mechanisms of various malignancies. This knowledge has paved the way for the development of personalized medicine approaches that target cancer-initiating cells, offering new hope for improved treatment outcomes [524]. Continued research in this field holds promise for further advancements in cancer prevention, diagnosis, and therapy, ultimately leading to better patient care and survival rates [525].

The relationship between cell-of-origin and cancer stem cells is a fundamental aspect of cancer biology. While the cell-of-origin initiates the oncogenic process, CSCs sustain and drive tumor growth, metastasis, and treatment resistance [512]. Recognizing the roles and characteristics of both cell types is vital for advancing our understanding of cancer and developing more precise and effective treatments. Cell-of-origin refers to the normal cell type from which cancer originates within the body [525]. Cancer typically arises when these normal cells accumulate genetic mutations or epigenetic changes that lead to uncontrolled growth and the development of a malignant tumor. The specific cell-of-origin can vary depending on the type of cancer and the tissue or organ in which it develops [521]. For instance, in lung cancer, the cell-of-origin may be a normal lung epithelial cell, while in breast cancer, it could be a mammary gland cell. The cell-of-origin plays a crucial role in shaping the characteristics of the resulting cancer, including its growth patterns and response to treatment. Cancer stem cells (CSCs), on the other hand, represent a specialized subset of cells within a tumor [526]. These cells are distinguished by their unique ability to self-renew and give rise to various cell types found within the tumor [525]. CSCs are thought to derive from either a small population of cancer cells that acquire additional mutations or from normal stem cells within the tissue that undergo dedifferentiation. They are often found at the apex of the tumor hierarchy and are responsible for driving tumor growth, initiating new tumors (tumor initiation), promoting metastasis, and conferring resistance to conventional cancer therapies [526]. One of the critical distinctions between cell-of-origin and CSCs lies in their roles in tumorigenesis [512]. The cell-of-origin is the initial cell that undergoes oncogenic events, leading to the formation of a cancerous lesion. In contrast, CSCs are responsible for the long-term maintenance of the tumor, playing a central role in its sustained growth and progression. Because CSCs possess self-renewal abilities and are highly resistant to treatment, they are often the culprits behind cancer recurrence after initial therapy [526]. Understanding the clinical implications of the cell-of-origin and CSCs is essential for cancer research and treatment strategies. Identifying the cell-of-origin provides insights into the tumor’s characteristics and behavior, helping clinicians tailor treatment approaches. For example, knowledge of the cell-of-origin can inform decisions about targeted therapies or treatments designed to eliminate the bulk of tumor cells derived from the cell-of-origin. In contrast, targeting CSCs has become a focal point in cancer therapy development [525]. Strategies aimed at eradicating or inhibiting CSCs are crucial for preventing tumor relapse and improving long-term treatment outcomes. By selectively targeting these stem-like cells within a tumor, researchers and clinicians hope to undermine the tumor’s ability to regenerate and resist treatment, ultimately leading to more effective cancer therapies [521].

Understanding the interplay between genetics, epigenetics and environment in tumorigenesis

There is increasingly evidence supporting that genetic and epigenetic mechanisms do not operate separately during tumorigenesis, they work together and are intertwined and take advantage of each other. Additionally, epigenetic changes may occur due to chance or as a result of environmental factors [30]. Ultimately, gene expression and abnormal phenotypes influenced by genetics, epigenetics and environment [31]. Although the genetic road to cancer or genome instability is relatively straightforward which occurred by mutation of tumor suppressors and/or oncogenes causes either a loss or gain of function and abnormal expression. Epigenetic pathways determine tumorigenesis through integrating numerous epigenetic variations, which are much more complex [31]. Epigenetics is based on the idea that interaction between the environment and the epigenome can alter phenotypes and contribute to disease susceptibility. It is noted that these changes could be transmitted down through generations [32]. Epigenetics is susceptible to environmental stressors. For example exposure to metals, chemical and xenobiotic compounds, air pollution, benzene, organic pollutants, and radiation can induce mutations that contribute to the development of cancer especially during embryonic stages, environmental factors have a more crucial impact on the genome and even can increase the risk of cancer in F₁, F₂ and F₃ generation [33]. The repression of tumor suppressor genes can also be induced by unhealthy habits, diet and pharmacological agents apart from chemical and physical environmental contributors. Several studies have shown how diet and food availability affect the epigenome in humans and how these epigenetic changes may be involved in several diseases in adulthood. There is an association between folate intake in the diet and epigenetic status in mammals [34] and has been related to methylation changes in colon cancer [35] and hyperhomocysteinemia [36]. Moreover, pharmacological treatments including those used for epilepsy, bipolar disorder, serious depression, migraine, and schizophrenia, complementary treatment for latent HIV infection can also induce genome-wide epigenetic changes [37]. In this regard, it remains unknown what part of the changes are caused by the interaction of the environment with the epigenome and what part are the result of just genetics. In order to, further research should focus on understanding the causes of these changes. Several of these questions will be answered in the future by next-generation technologies.

The role of stem cells in tumorigenesis

Stem cells have been used for over 30 years for cancer treatment via tissue regeneration and as delivery vehicles. Research communities have been directed towards advancement in the field of cancer research following the recent introduction of cancer stem cells as the backbone of cancer development [7]. Stem cells are undifferentiated and have the ability to self-renew and proliferate for longer periods, as well as produce multiple types of cells [38]. In a recent investigation led by Saha et al., the primary focus was on the development of specially modified surfaces to improve the cultivation of human pluripotent stem cells (hPSCs) within a completely defined environment [527]. The study’s objective was to address the shortcomings associated with traditional culture systems reliant on feeder cells and establish a standardized and reproducible platform for hPSC cultivation. Figure 9 underscores the crucial role of chemically optimized surfaces in fostering the growth of more undifferentiated hPSCs compared to substrates with feeder cells, underscoring the superiority of these engineered surfaces. Figure 9 illustrates the physical changes applied to the polystyrene substrates, encompassing both chemical and geometrical modifications, which were pivotal in enhancing their performance. To further advance the engineered surfaces, the study employed computational modeling, as depicted in Fig. 9, to simulate and predict cell behavior on substrates featuring UV-patterned spots, aiding in the design and enhancement of these surfaces. Figure 9 demonstrates the successful long-term cultivation of stem cells on these UV-patterned substrates, underscoring their suitability for maintaining hPSCs in a healthy, undifferentiated state. Additionally, Fig. 9 provides experimental findings and visual proof supporting the effective reprogramming and genetic modification of hPSCs utilizing the UV-patterned substrates, highlighting their potential utility in disease modeling and personalized medicine applications. Finally, Fig. 9 illustrates the utilization of UV-patterned substrates to facilitate the transfer of individual hPSCs, further emphasizing the practical advantages offered by these engineered surfaces. Oncogenes and anti-oncogenes play a key role in initiation of cancer which is followed by the conversion normal stem cells into cancer cells under certain environmental conditions [39]. In general, stem cells reveal various levels of differentiation potential, starting with totipotency, pluripotency, multipotency, oligopotency and finally unipotency/monopotency [528]. The role of stem cells in tumorigenesis encompasses the concept of Cancer Stem Cells (CSCs), which represent a subset of cancer cells sharing characteristics with normal stem cells [247]. CSCs play a pivotal role in driving uncontrolled tumor progression through their abilities in self-renewal [528]. Although it’s worth noting that unlike normal stem cells, not all CSCs exhibit pluripotent differentiation potential, which refers to the capacity for differentiation into all three germ layers [247]. Cancer stem cells are hypothesized to cause metastasis and resistance to therapy, as well as post-operative recurrences. As a result, targeting CSCs may provide new treatments for cancer patients [42]. Recently, many molecular mechanisms have been elucidated that explain tumorigenesis in cancer and stem cell self-renewal [43]. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. The following are signaling cascades that are frequently dysregulated in cancer: Ras/Raf/MEK/ERK (MAPK) as a major determinant in the control of proliferation, survival, and differentiation. And the PTEN/PI3K/AKT/mTOR pathways. Activating mutations of Ras and Raf frequently leading to activation of their downstream targets MEK1/2 and ERK1/2 [44]. Similarly, in the PI3K/AKT/mTOR pathway, mutation/inactivation of PTEN resulting in activation of PI3K and its downstream targets AKT and mTOR [45]. Wnt signaling plays a crucial role in regulating endogenous stem cells as well as tissue development and homeostasis. Cancer stem cells are influenced by abnormal Wnt signaling, which directly contributes to the development and maintenance of many cancers [529]. The Hedgehog (Hh) signaling pathway with three proteins which is involved in activation (Hedgehog (Hh) ligand, Patched (Ptch) and Smoothened (Smo)) is a conserved evolutionary pathway that transmits signals from the cell membrane to the nucleus. It is critical for the regeneration of tissue and is normally inactive or poorly active. The Hh signaling pathway may be involved in various stages of carcinogenesis, as well as in early tumor stages and metastatic tumors [47]. Besides being masses of malignant cells, tumorigenesis is also affected by changes in the tumor microenvironment (TME). Tumor microenvironments are formed by interactions between malignant and non-transformed cells like endothelial and immune cells, MSCs, and fibroblast-like stroma cells, the tumor vasculature and lymphatics, as well as fibroblasts, pericytes and sometimes adipocytes [48]. Essentially, this microenvironment contribute to maintain tumor phenotypes by triggering self-renewal of CSCs, stimulating angiogenesis, and recruiting cells that produce additional factors that drive metastasis and invasiveness of tumor cells [49]. Over several decades, cancer biomarkers like long non-coding RNAs as one of the most important regulatory factors can be used effectively for diagnosis, therapy, and prognosis via their role in identification cancer stem cells and their related microenvironments. They are detectable in liquid biopsy samples such as plasma, saliva, and urine [50]. In both developed and developing countries, cancer remains a significant economic and social burden. It is well known that cancer contributes to increased mortality, poor health, and high healthcare costs in the long run. Therefore, further research is imperative to fully understand the mechanisms underlying tumorigenesis and to develop novel therapeutic strategies to promote the health and well-being of cancer patients [51].

The iPSCs as a model for tumorigenesis

The iPSCs have emerged as a valuable model for studying tumorigenesis. Their ability to differentiate into cancer cells, their genetic fidelity to patient-derived cells, and their capacity to recapitulate tumorigenic properties make them an ideal tool for investigating the complex processes underlying tumor initiation, progression, and response to therapy. iPSCs offer a unique opportunity to study the molecular and genetic changes occurring during tumorigenesis, providing insights into the key factors driving tumor development [530]. As research in this field advances, iPSCs hold great promise for advancing our understanding of cancer biology and paving the way for personalized and targeted cancer therapies [531]. Moreover, iPSCs offer the advantage of being able to model the early stages of tumorigenesis, which is often challenging to study using traditional cancer cell models [532]. By inducing the differentiation of iPSCs into specific cell lineages relevant to the type of cancer being investigated, researchers can gain insights into the initial cellular events that lead to tumor formation [532]. This includes the acquisition of cancer-specific mutations, epigenetic modifications, and alterations in signaling pathways [533]. iPSCs can provide a time-resolved snapshot of the molecular changes occurring during early carcinogenesis, offering a valuable tool for identifying novel biomarkers and potential therapeutic targets [534, 535]. In addition to their potential in studying cancer initiation, iPSCs can be employed to investigate the dynamic nature of tumor progression[536]. By generating iPSC-derived cancer cells at different stages of tumor development, researchers can observe and analyze the molecular changes that occur as the cancer progresses [537]. This longitudinal approach enables the identification of key genetic and epigenetic events driving tumor growth, invasion, and metastasis [538]. Furthermore, iPSCs can be used to model the heterogeneity observed within tumors, allowing researchers to study the subpopulations of cancer cells with distinct properties, such as stem-like cells or cells with drug-resistant phenotypes [539]. This information is crucial for developing targeted therapies that can effectively eradicate different cancer cell populations. The use of iPSCs in tumorigenesis research also extends to the field of drug discovery and personalized medicine [540]. iPSCs derived from patients with specific types of cancer can be employed in drug screening assays to evaluate the efficacy and toxicity of potential therapeutic agents [541]. This approach holds promise for developing personalized treatment strategies, as iPSCs can be used to predict patient-specific responses to different drugs. By analyzing the drug response profiles of iPSC-derived cancer cells, researchers can identify individualized treatment regimens tailored to each patient’s unique genetic and cellular characteristics, ultimately improving treatment outcomes [540]. While the potential of iPSCs in tumorigenesis research is immense, several challenges and limitations need to be addressed. One challenge is the efficient and reliable generation of iPSCs from patient samples, as this process can be time-consuming and may have variable success rates. Additionally, ensuring the faithful differentiation of iPSCs into the desired cancer cell types can be complex, requiring the optimization of differentiation protocols [542]. Furthermore, the long-term stability and genetic integrity of iPSCs and their differentiated derivatives need to be carefully monitored to avoid unintended genetic or epigenetic changes that could impact the reliability of the model [542]. The iPSCs represent a powerful and versatile model for studying tumorigenesis. Their ability to recapitulate tumorigenic properties, investigate molecular and genetic changes, and model the heterogeneity of tumors makes them a valuable tool for advancing our understanding of cancer development and progression. Furthermore, iPSCs have the potential to revolutionize drug discovery and personalized medicine by enabling the development of tailored therapies based on individual patient characteristics[543]. As researchers continue to overcome challenges and refine techniques in iPSC research, the promising potential of iPSCs for tumorigenesis and therapy will be further realized, paving the way for improved diagnostics, treatments, and patient outcomes in the field of oncology.

The potential of iPSCs to study tumorigenesis

iPSCs have emerged as a promising resource for delving into the origins of cancer, a multifaceted ailment stemming from a combination of genetic, epigenetic, and environmental influences [532].

Tumorigenesis is a complex series of events where changes occur in how genes are expressed, how proteins function, and how cells behave, all culminating in the formation of cancerous tumors [536]. While there have been notable advancements in the field of cancer research, several facets of how tumors develop are still not fully comprehended. This lack of understanding presents difficulties in crafting successful treatments for various cancer forms. iPSCs, on the other hand, originate from mature somatic cells that have undergone reprogramming to attain a pluripotent state, enabling them to transform into any cell type within the body [539]. The capability to create iPSCs from individuals afflicted with diverse forms of cancer offers scientists a potent means to investigate the molecular alterations that transpire during the development of tumors. iPSCs can be transformed into various cell categories pertinent to cancer, including cancer stem cells, which are thought to play a pivotal role in the onset and advancement of numerous cancer types [534, 535]. Analyzing the actions of cancer stem cells that originate from iPSCs allows scientists to uncover the fundamental processes driving the onset and advancement of cancer. Beyond serving as a distinct method for investigating how tumors form, iPSCs can serve as valuable tools for screening potential drugs and tailoring medical treatments. iPSCs can be generated from individuals with various cancer types, facilitating the creation of customized cancer models specific to each patient [536]. These models can be used to screen potential therapies, identify drugs that are most effective in specific patient populations, and develop personalized treatment plans. This approach has the potential to significantly improve cancer treatment outcomes by tailoring therapies to individual patients based on their unique genetic makeup and cancer characteristics [532]. Another potential application of iPSCs in cancer research is the development of immunotherapies. Immunotherapies are a promising approach to cancer treatment that involves harnessing the patient’s immune system to fight cancer [539]. Nonetheless, the difficulty in creating successful immunotherapies arises from the intricate interplay between cancer cells and the immune system. iPSCs offer a potential solution by allowing for the creation of patient-specific immune cells, facilitating the development of customized immunotherapeutic approaches [536]. These therapies have the potential to be more effective and have fewer side effects than current approaches to cancer treatment. Despite the potential of iPSCs in cancer research, there are still many challenges that must be addressed [532]. One of the main challenges is the tumorigenic properties of iPSCs. iPSCs have been shown to have a higher propensity to form tumors than other types of stem cells, which could limit their use in cancer research and therapy [536]. However, recent advances in iPSC technology have led to the development of safer and more efficient methods for generating iPSCs, which could help to address this challenge. Another challenge is the ethical and legal considerations surrounding iPSC research [532]. The use of human embryonic stem cells in research has been controversial due to ethical concerns, but iPSCs offer a viable alternative that avoids these issues. However, there are still ethical and legal considerations that must be addressed, such as ensuring that iPSC research is conducted in an ethical and responsible manner and that patient privacy is protected [536]. In a recent investigations provided the study delved into the molecular and functional similarities between differentiated cells originating from induced pluripotent stem cells (iPSCs) and embryonic stem cells derived through somatic cell nuclear transfer (SCNT), known as nt-ESCs [544]. The research compared the differentiation processes and traits of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically matched sets of iPSCs, nt-ESCs, and in vitro fertilization embryo-derived ESCs (IVF-ESCs). The study revealed that iPSC-derived cells displayed comparable lineage gene expression, cellular diversity, physiological characteristics, and metabolic functions when compared to their corresponding nt-ESC counterparts. Figure 10 illustrates the cardiac differentiation process across various human stem cell types, emphasizing the role of iPSCs. Additionally, Fig. 10 demonstrates the generation of endothelial cells from different pluripotent stem cell sources. The RNA-seq analysis results in Fig. 10 offered insights into the global gene expression profiles of PSCs, PSC-CMs, and PSC-ECs. Furthermore, Fig. 10 provides a comprehensive examination of DNA methylation patterns in these cell types using RRBS-seq. These findings suggest that iPSCs can effectively replace nt-ESCs in generating patient-specific differentiated cells, facilitating disease modeling and preclinical drug testing. Figure 10 identifies consistent differentially methylated regions in undifferentiated PSCs and fully differentiated cells, while Fig. 10 illustrates the impact of doxorubicin-induced toxicity on CMs derived from various sources, including iPSCs, nt-ESCs, and IVF-ESCs. These results underscore the potential of iPSCs in regenerative medicine and emphasize the significance of considering genetic composition when assessing the molecular and functional attributes of differentiated cells. The iPSCs offer significant potential for studying tumorigenesis, developing new cancer therapies, and improving patient outcomes [545, 546]. The ability to generate iPSCs from patients with different types of cancer provides a powerful tool for studying the molecular changes that occur during cancer initiation and progression. iPSCs can also be used for drug screening, personalized medicine, and the development of immunotherapies [24]. While there are still challenges that must be addressed, the potential benefits of iPSC research in tumorigenesis are significant and warrant continued investment in this field [543]. Moreover, iPSCs hold promise for early detection of cancer. Detecting cancer at an early stage is crucial for improving patient outcomes, as it allows for timely intervention and treatment. iPSCs can be utilized to create disease models that mimic the early stages of cancer development, providing valuable insights into the molecular and cellular changes that occur during this critical phase [545, 546]. By studying these models, researchers can identify biomarkers and develop innovative diagnostic tools for the early detection of cancer. This can lead to more effective screening strategies and the ability to detect cancer before it progresses to an advanced stage [543]. Furthermore, iPSCs offer a valuable platform for understanding the role of epigenetic modifications in tumorigenesis. Epigenetic alterations, such as DNA methylation and histone modifications, play a significant role in the development and progression of cancer. iPSCs can be reprogrammed from patient-derived somatic cells, capturing the epigenetic marks present in the original cells [545, 546]. By comparing iPSCs derived from healthy individuals and those with cancer, researchers can identify specific epigenetic modifications associated with tumorigenesis. This knowledge can lead to the development of targeted therapies aimed at reversing or inhibiting these cancer-associated epigenetic changes [24]. Additionally, iPSCs provide an opportunity for studying the tumor microenvironment and its influence on tumorigenesis. The tumor microenvironment consists of various cell types, including immune cells, fibroblasts, and blood vessels, which interact with cancer cells and impact tumor growth and metastasis. iPSCs can be differentiated into these different cell types, allowing researchers to recreate a simplified version of the tumor microenvironment in the laboratory [543]. By studying the interactions between iPSC-derived tumor cells and the surrounding microenvironment, researchers can gain insights into the complex signaling pathways and cellular crosstalk involved in cancer progression. This knowledge can aid in the development of novel therapeutic strategies targeting the tumor microenvironment [545, 546].

Comparison of iPSCs with traditional cancer cell models

The iPSCs have emerged as a promising tool in cancer research, providing unique advantages compared to traditional cancer cell models [548]. Comparing iPSCs to traditional cancer cell models highlights the unique advantages and limitations of each model. While traditional cancer cell models have been critical in advancing our understanding of cancer biology and drug discovery [545, 546], iPSCs offer novel capabilities that enhance our ability to study cancer development and progress towards personalized medicine [24]. By leveraging the strengths of both models, researchers can continue to make progress in cancer research, ultimately leading to more effective therapies and improved patient outcomes. While traditional cancer cell models, such as established cancer cell lines and patient-derived xenografts (PDX), have been instrumental in advancing our understanding of cancer biology and drug discovery, iPSCs offer distinct benefits that enhance our ability to study tumorigenesis and develop effective therapies [24, 549]. One key advantage of iPSCs is their ability to recapitulate the genetic and epigenetic diversity observed in tumors [550]. Traditional cancer cell models often represent a specific subtype or clone of cancer cells, limiting their applicability to studying the heterogeneity seen in clinical tumors [546]. In contrast, iPSCs can be generated from various somatic cells, including cancer cells, allowing for the generation of iPSC lines that reflect the genomic and epigenomic alterations found in individual patients [551, 552]. This enables researchers to study the effects of specific mutations and alterations on cancer development and progression, offering valuable insights into personalized medicine approaches [552]. Moreover, iPSCs have the unique ability to differentiate into various cell types, including different lineages of cancer cells. This feature allows researchers to generate diverse populations of cancer cells that mirror the heterogeneity within tumors [553]. By differentiating iPSCs into specific cancer cell lineages, researchers can investigate the molecular changes associated with cancer progression and metastasis as well as identifying potential therapeutic targets [554]. In addition to their capacity for differentiation, iPSCs can also be utilized to model early stages of cancer development [125]. Traditional cancer cell models often represent advanced stages of the disease, limiting the ability to study the initial events leading to cancer formation [543]. iPSCs, on the other hand, can be reprogrammed from somatic cells obtained from healthy individuals, allowing researchers to study the early stages of carcinogenesis [554]. This provides a unique opportunity to uncover the molecular changes and cellular processes that drive cancer initiation, offering insights into early detection and prevention strategies [555]. Furthermore, iPSCs offer a powerful tool for drug screening and personalized therapy development. Traditional cancer cell models have been extensively used in high-throughput drug screening assays. However, these models often fail to accurately predict drug responses in patients, partly due to their limited representation of patient-specific genetic backgrounds [556]. iPSCs, with their ability to capture patient-specific genetic information, can be utilized to generate personalized cancer cell models. By deriving iPSCs from patient samples and differentiating them into cancer cells, researchers can create an individualized platform for testing drug efficacy and toxicity, aiding in the development of personalized treatment regimens [548]. Despite these advantages, there are challenges and limitations associated with iPSCs compared to traditional cancer cell models. One major challenge is the complexity and cost of iPSC generation and maintenance [33]. The reprogramming process itself is time-consuming and requires specialized expertise. Additionally, the long-term culture of iPSCs can lead to genomic instability and alterations in their epigenetic landscape, potentially affecting their suitability as cancer models [542]. These technical challenges need to be addressed to ensure the reliability and reproducibility of iPSC-based cancer research [542]. Moreover, ethical considerations surrounding the use of iPSCs should be taken into account. The generation of iPSCs involves the manipulation of human embryos or the reprogramming of adult somatic cells, raising ethical concerns and legal regulations. These ethical considerations should be carefully addressed to ensure the responsible and ethical use of iPSCs in cancer research and therapy development [557]. In conclusion, iPSCs offer distinct advantages when compared to traditional cancer cell models, enabling researchers to study the complexity and heterogeneity of tumors more effectively [549]. Their ability to recapitulate the genetic and epigenetic diversity of tumors, differentiate into multiple cell lineages, model early stages of carcinogenesis, and generate personalized cancer cell models makes iPSCs a powerful tool in cancer research [125, 540]. However, challenges and limitations such as technical difficulties and ethical considerations need to be addressed to ensure the reliability and ethical use of iPSCs in cancer research and therapy development. Table 7 presents a comprehensive overview of the advantages and limitations associated with two prominent cancer research models: iPSCs and traditional cancer cell models.

Table 7 Comprehensive analysis of advantages and limitations of iPSCs and traditional cancer cell models

Full size table

The use of iPSCs to study the tumorigenic properties of cancer cells

The iPSCs have emerged as a powerful tool in the study of cancer biology. With their ability to differentiate into various cell types and self-renew, iPSCs offer a unique model for investigating the tumorigenic properties of cancer cells [559]. Tumorigenic properties refer to the ability of cancer cells to form tumors. Cancer cells can acquire these properties through a variety of molecular changes, such as alterations in gene expression, mutations, and changes in signaling pathways [560]. By studying these properties, researchers can gain insights into the mechanisms of cancer development and identify potential targets for cancer therapy [561]. One of the challenges in studying cancer is the heterogeneity of tumor cells. Cancer cells are genetically and phenotypically diverse, even within the same tumor [562]. This heterogeneity makes it difficult to accurately characterize the properties of cancer cells and develop effective therapies [562]. iPSCs offer a solution to this challenge by providing a homogeneous population of cells with a known genetic background. iPSCs can be generated from patient-derived somatic cells, including cancer cells. These iPSCs retain the genetic and epigenetic alterations found in the original cells and can be differentiated into various cell types, including cancer cells [552]. By comparing the properties of iPSC-derived cancer cells with those of the original cancer cells, researchers can identify changes in gene expression and signaling pathways that contribute to tumorigenesis. One approach to studying the tumorigenic properties of cancer cells using iPSCs involves the generation of tumor organoids [563]. Tumor organoids are three-dimensional cultures of cells that mimic the structure and function of a tumor [563]. iPSC-derived cancer cells can be used to generate tumor organoids that closely resemble the original tumor [368]. These organoids can be used to study the properties of the tumor, such as growth rate, invasion, and response to therapy [564]. Another approach involves the use of iPSC-derived cancer cells in xenograft models. Xenograft models involve the transplantation of human cancer cells into immunocompromised mice [565]. iPSC-derived cancer cells can be used to generate xenograft models that closely resemble the original tumor [565]. These models can be used to study the properties of the tumor in vivo, such as growth rate, invasion, and response to therapy. The use of iPSCs to study the tumorigenic properties of cancer cells has several potential implications for cancer therapy. By identifying the molecular changes that contribute to tumorigenesis, researchers can develop targeted therapies that selectively inhibit these changes [566]. iPSC-derived cancer cells can also be used to screen drugs for their efficacy in killing cancer cells. This approach has the potential to identify new drugs and drug combinations that are effective in treating cancer [5]. Additionally, iPSC-derived cancer cells can be used in personalized medicine [24]. By generating iPSCs from patient-derived cells and differentiating them into cancer cells, researchers can create a patient-specific model of the tumor. This model can be used to identify the most effective treatment for the patient, based on the properties of their tumor [24]. Despite the potential benefits of using iPSCs to study the tumorigenic properties of cancer cells, there are several limitations and challenges. One challenge is the cost and technical expertise required to generate and maintain iPSCs [567]. Additionally, iPSC-derived cancer cells may not fully capture the complexity of the original tumor, as they may lack the microenvironmental cues and interactions with other cell types that contribute to tumorigenesis [490]. Another limitation is the potential for iPSC-derived cancer cells to form tumors when transplanted into mice [506]. iPSCs have been shown to have tumorigenic potential, and this risk is heightened when iPSCs are differentiated into cancer cells. Therefore, careful consideration and rigorous characterization are necessary when using iPSC-derived cancer cells in xenograft models or transplantation experiments [506]. Despite these challenges, the use of iPSCs to study the tumorigenic properties of cancer cells holds great promise. The ability to generate patient-specific models of tumors allows for personalized approaches to cancer therapy [24]. By understanding the molecular changes that drive tumorigenesis, researchers can develop targeted therapies that are tailored to individual patients, increasing the chances of successful treatment outcomes [24]. Furthermore, the use of iPSC-derived cancer cells in drug screening can accelerate the discovery and development of new cancer therapies [568]. Traditional drug screening methods often fail to accurately predict the response of human tumors due to the limitations of using immortalized cancer cell lines [569]. iPSC-derived cancer cells provide a more representative model that better reflects the complexity and heterogeneity of human tumors, increasing the likelihood of identifying effective treatments [559]. In addition to their potential in drug discovery, iPSCs offer valuable insights into the early detection and prevention of cancer. By studying the properties of iPSC-derived cancer cells, researchers can identify biomarkers and molecular signatures associated with early stages of tumorigenesis. This knowledge can contribute to the development of non-invasive diagnostic tools for the early detection of cancer, enabling timely interventions and improved patient outcomes. The iPSCs have opened up new avenues for studying the tumorigenic properties of cancer cells. Their ability to recapitulate the genetic and epigenetic alterations found in cancer cells, combined with their potential for differentiation into various cell types, provides a valuable platform for investigating the mechanisms of tumorigenesis [570]. The use of iPSC-derived cancer cells in tumor organoids and xenograft models allows for the study of tumor growth, invasion, and response to therapy in a controlled and reproducible manner [571]. Moreover, iPSCs have the potential to drive advancements in personalized medicine, drug discovery, and early cancer detection. However, challenges such as cost, technical expertise, tumor heterogeneity, tumorigenicity, and ethical considerations must be addressed to fully harness the potential of iPSCs in cancer research [507, 572]. Continued investment in iPSC research and collaboration between scientists, clinicians, and ethicists is crucial to unlock the full potential of iPSCs in understanding and treating cancer.

The use of iPSCs to study the molecular and genetic changes during tumorigenesis

One recent study published in the journal Cell Stem Cell demonstrated the potential of iPSCs in cancer research by using them to study the molecular changes that occur during the progression of colorectal cancer. The researchers generated iPSCs from both healthy individuals and patients with early-stage colorectal cancer and then differentiated them into intestinal organoids. Using this model, they were able to identify key molecular changes that occur during the early stages of colorectal cancer development, including alterations in the Wnt signaling pathway and changes in the expression of genes involved in cellular differentiation. They also observed an increase in the number of cancer stem cells present in the organoids derived from cancer patients, which could contribute to the development and progression of the disease [573]. Another study published in the journal Nature Communications utilized iPSCs to study the genetic changes that occur during the development of lung cancer. The researchers used iPSCs derived from patients with lung cancer to create lung organoids that closely resemble the cellular architecture of human lung tissue. By comparing the genetic profiles of the lung organoids derived from healthy individuals and patients with lung cancer, the researchers were able to identify mutations in several key genes that are frequently mutated in lung cancer, including TP53, KRAS, and EGFR. They also observed changes in the expression of genes involved in cell adhesion and signaling pathways that are known to play a role in cancer development [574]. These studies demonstrate the potential of iPSCs in cancer research, particularly in understanding the early molecular and genetic changes that occur during tumorigenesis. iPSC-derived models can provide a more accurate representation of human disease than traditional cell culture models and offer a more cost-effective and ethical alternative to animal models [543]. Additionally, iPSCs have the potential to be used in the development of personalized cancer therapies. By generating iPSCs from individual patients, researchers can create organoids that closely resemble the patient’s own tissue, allowing for more accurate testing of potential treatments and the development of personalized therapeutic approaches [575,576,577]. However, there are also challenges associated with the use of iPSCs in cancer research. One major limitation is the potential for iPSCs to harbor genetic abnormalities or epigenetic changes that could affect their behavior and skew the results of experiments. Researchers must carefully screen and characterize iPSCs to ensure that they are of high quality and free from abnormalities before using them in experiments [542]. Furthermore, there are ethical and legal considerations associated with the use of iPSCs, particularly when it comes to the creation and use of iPSCs derived from human embryos [557]. Researchers must navigate complex regulatory frameworks and ensure that they are conducting their research in an ethical and responsible manner [557]. Despite these challenges, the use of iPSCs in cancer research holds tremendous promise for advancing our understanding of tumorigenesis, identifying new therapeutic targets, and developing personalized treatments for the disease. With continued investment and research, iPSCs have the potential to revolutionize cancer research and improve outcomes for patients around the world [574].

Applications of iPSCs in tumorigenesis

The iPSCs have emerged as a powerful tool in cancer research, offering diverse applications in various aspects of tumorigenesis [507]. The utilization of patient-derived iPSCs has undeniably emerged as a powerful tool in the realm of cancer research. Various research groups across the globe have undertaken compelling investigations into the intricate relationship between germline mutations and the occurrence of cancer. Through meticulous experimentation, these dedicated teams have harnessed the potential of iPSCs to unveil profound insights into the underlying mechanisms of cancer development and, in turn, drive forward the frontiers of drug discovery [572]. One notable aspect of this vibrant field is the considerable body of work that has culminated in critical findings regarding cancer etiology and progression. The omission of a comprehensive review of these pivotal discoveries by the authors is a regrettable oversight. These findings represent a cornerstone of contemporary iPSC-based cancer research, providing valuable benchmarks for the broader scientific community. By neglecting to acknowledge and incorporate these contributions, the authors risk presenting an incomplete analysis of the field, leaving gaps in the understanding of the complex interplay between germline mutations and cancer [574]. To ensure a well-rounded and robust assessment of the iPSC-based cancer research landscape, it is imperative for the authors to address this significant deficiency in their work. By integrating these important contributions into their analysis, the authors can enrich their study and provide a more holistic perspective on the transformative potential of patient-derived iPSCs in deciphering the mysteries of cancer. This collaborative and inclusive approach will not only benefit the authors’ work but also foster a deeper understanding of the broader scientific community’s collective efforts in unraveling the complexities of cancer biology [542]. Moreover, the incorporation of these crucial findings from various research groups will enhance the overall scientific rigor of the authors’ analysis. By acknowledging the extensive body of work conducted in the field of iPSC-based cancer research, the authors can strengthen the foundation upon which their research is built. This inclusivity will not only validate the efforts of their peers but also elevate the credibility and comprehensiveness of their own work [574]. Additionally, the integration of these research findings can provide a broader context for the authors’ work, allowing readers and fellow researchers to appreciate the interconnectedness of different studies within this multidisciplinary field. It can also help identify potential gaps or areas that require further investigation, fostering a collaborative environment for future research endeavors [575,576,577].

The use of iPSCs in developing new cancer therapies

The iPSCs have emerged as a promising tool in the development of new cancer therapies, offering unprecedented opportunities to advance our understanding of tumorigenesis and transform the landscape of cancer treatment [578, 579]. These remarkable cells, which are derived from adult somatic cells through a process of reprogramming, possess the ability to differentiate into various cell types, including those relevant to cancer, making them an invaluable resource for studying disease mechanisms and developing novel therapeutic strategies [24, 580, 581]. Table 8 presents a comprehensive overview of the current iPSC-based cancer therapies that have emerged as promising strategies in the field of oncology. One of the key advantages of iPSCs in cancer therapy lies in their ability to provide a robust and patient-specific model for studying tumorigenesis [564, 577]. By reprogramming cells from cancer patients, researchers can generate iPSCs that carry the genetic and epigenetic signatures of the individual’s tumor [550]. These iPSCs can then be differentiated into the specific cell types affected by cancer, allowing for detailed investigation of the molecular changes and abnormalities associated with the disease [582]. This personalized approach enables researchers to gain insights into the underlying mechanisms of cancer development, identify novel therapeutic targets, and tailor treatment strategies to individual patients [24, 581, 583]. Furthermore, iPSCs offer a unique platform for drug screening and the development of targeted therapies [540, 584]. Traditional cancer cell lines and animal models often fail to accurately replicate the complexity and heterogeneity of human tumors, limiting their predictive value in preclinical studies [545, 546]. iPSC-derived cancer cells, on the other hand, can more faithfully recapitulate the genetic and phenotypic characteristics of the patient’s tumor, making them an ideal tool for testing the efficacy and toxicity of potential therapeutics [576, 585]. Through high-throughput screening approaches, large libraries of compounds can be screened against iPSC-derived cancer cells, leading to the identification of novel drug candidates and personalized treatment options [548, 586]. Immunotherapies, which harness the body’s immune system to target and eliminate cancer cells, have revolutionized cancer treatment in recent years [555, 587]. iPSCs hold great promise in this field as well, as they can be engineered to express tumor-specific antigens and used as a source for generating patient-specific immune cells. By differentiating iPSCs into immune cells, such as T cells or natural killer cells, researchers can create a personalized immunotherapy approach that is tailored to the patient’s specific tumor antigens [588,589,590]. This personalized immunotherapy has the potential to enhance the efficacy of treatment while minimizing off-target effects, leading to more targeted and effective cancer therapies [104, 531, 581, 591]. Moreover, iPSCs can be utilized for cancer early detection and diagnosis. Through their ability to differentiate into various cell types, including those found in tumors, iPSCs can be employed to generate specific cell populations that mimic the early stages of cancer development [533, 539, 592]. By studying the molecular changes and aberrant signaling pathways present in these iPSC-derived cancer cells, researchers can gain valuable insights into the early detection and diagnosis of cancer [267, 554, 593]. This knowledge can then be translated into the development of innovative diagnostic tools and biomarkers for improved cancer screening and early intervention [125]. Despite the tremendous potential of iPSCs in cancer therapy, several challenges and limitations need to be addressed. One major hurdle is the risk of tumorigenicity associated with the transplantation of iPSCs or their derivatives [594, 595]. The pluripotent nature of iPSCs renders them capable of uncontrolled growth and potential tumor formation. Therefore, stringent quality control measures and extensive characterization of iPSCs and their differentiated progeny are essential to ensure their safety and efficacy in clinical applications [542, 594].

Table 8 Current iPSC-based cancer therapies

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The use of iPSCs in drug screening and development

The use of iPSCs in drug screening and development has emerged as a promising avenue in the field of medicine. iPSCs, which are derived from adult cells reprogrammed to possess pluripotency, offer a unique platform for studying disease mechanisms and evaluating the efficacy and safety of potential drugs [568, 575, 584]. This paragraph will delve into the advantages of iPSCs in drug screening and development, highlighting their potential to revolutionize the process of discovering new therapies. One of the key advantages of using iPSCs in drug screening is their ability to recapitulate disease phenotypes in a controlled laboratory setting [575]. By reprogramming patient-specific cells, researchers can generate iPSCs that carry the genetic signature of a particular disease [553, 611]. These disease-specific iPSCs can then be differentiated into relevant cell types affected by the disease, such as neurons for neurodegenerative disorders or cardiomyocytes for cardiovascular diseases [611, 612]. This approach enables scientists to model the disease in a dish, allowing for the identification of novel drug targets and the screening of potential therapeutics in a more physiologically relevant context [576, 613]. Furthermore, iPSCs provide a valuable tool for studying rare diseases or conditions where access to patient samples is limited. These cells can be generated from easily accessible somatic cells, such as skin cells or blood cells, and then differentiated into the desired cell types [21]. This not only circumvents the need for invasive procedures to obtain patient-specific samples but also allows for the creation of large, diverse libraries of disease-specific iPSCs [556, 576, 614]. These libraries can be shared among researchers, fostering collaboration and accelerating drug discovery efforts for conditions that have previously been challenging to study. The use of iPSCs in drug screening also holds promise for personalized medicine. iPSCs can be derived from individual patients, allowing for the development of tailored therapies based on a patient’s specific genetic background. This approach has the potential to transform the field of oncology, as it can aid in the identification of personalized treatment strategies for cancer patients. By generating iPSCs from tumor cells, researchers can create a personalized model that mimics the unique characteristics of a patient’s cancer [15, 615, 616]. This model can be used to screen a variety of drugs and identify the most effective treatment options, thereby improving patient outcomes and reducing unnecessary exposure to ineffective therapies [616]. In addition to personalized medicine, iPSCs offer an invaluable resource for drug toxicity testing [617,618,619]. Many promising drug candidates fail during the later stages of development due to unexpected toxic effects on vital organs or systems. By using iPSCs to generate different cell types, researchers can evaluate the potential toxicity of drugs in a controlled and reproducible manner [619]. For instance, iPSC-derived liver cells can be used to assess the hepatotoxicity of drug candidates [620], while iPSC-derived cardiomyocytes can provide insights into potential cardiac side effects [621, 622]. This early identification of drug toxicity can help pharmaceutical companies make informed decisions about which compounds to advance in the drug development pipeline, ultimately reducing the risk of adverse effects in clinical trials and improving patient safety [622]. Moreover, iPSCs enable the screening of existing drugs for new therapeutic applications [623]. Repurposing known drugs for different diseases can significantly reduce the time and cost associated with developing new treatments. iPSCs provide a reliable platform for evaluating the efficacy of approved drugs in various disease models. By exposing iPSC-derived disease-relevant cells to a library of known compounds, researchers can identify drugs that exhibit unexpected therapeutic effects or synergistic interactions with existing therapies [624]. This approach has the potential to uncover new treatment options for a range of diseases, opening up avenues for drug repurposing and expanding the therapeutic arsenal available to clinicians. The use of iPSCs in drug screening and development holds tremendous potential to transform the field of medicine [568, 611]. These versatile cells allow for the generation of disease-specific models, personalized medicine approaches, toxicity testing, and drug repurposing efforts. iPSCs provide a unique platform for studying disease mechanisms and evaluating the efficacy and safety of potential drugs [535, 623]. By reprogramming patient-specific cells, researchers can create disease-specific iPSCs that accurately recapitulate the genetic signature and phenotypic characteristics of various diseases [594, 625, 626]. The ability to generate disease-specific cell types from iPSCs allows researchers to study the underlying mechanisms of diseases in a controlled laboratory environment [622]. This approach provides valuable insights into disease progression, identifying key molecular pathways and targets that can be exploited for therapeutic interventions [609, 614]. By screening potential drugs on iPSC-derived disease models, researchers can assess their effectiveness in restoring normal cellular function and halting disease progression [627]. This screening process helps prioritize drug candidates for further development, increasing the efficiency of the drug discovery process and reducing the reliance on animal models. Personalized medicine is another area where iPSCs have the potential to revolutionize drug development. By generating iPSCs from individual patients, it is possible to create patient-specific models that accurately reflect their genetic makeup and disease characteristics. This personalized approach allows for tailored treatment strategies, optimizing therapeutic outcomes and minimizing adverse effects [241, 617]. iPSCs can be used to screen a variety of drugs on patient-specific disease models, identifying the most effective treatments for individual patients. This approach has particular relevance in the field of oncology, where tumor-derived iPSCs can be utilized to screen a range of targeted therapies and chemotherapeutic agents, enabling clinicians to make informed treatment decisions based on the unique biology of a patient’s tumor [15]. One of the critical advantages of iPSCs in drug screening is their potential to predict drug toxicity and side effects. Adverse drug reactions and toxic effects are significant challenges in drug development. iPSCs offer a reliable and scalable platform for assessing drug toxicity by differentiating them into organ-specific cell types [585, 617, 618]. By subjecting iPSC-derived cells to potential drug candidates, researchers can evaluate their safety profiles, identifying any potential toxic effects on specific organs or systems [620]. With ongoing research and advancements in iPSC technology, the integration of iPSCs in drug discovery pipelines holds great promise for accelerating the development of safe and effective treatments for a wide range of diseases.

The use of iPSCs in personalized medicine

The use of iPSCs in personalized medicine has emerged as a groundbreaking approach with the potential to revolutionize patient care [568, 575, 584]. Personalized medicine aims to tailor medical treatments to individual patients based on their unique genetic, epigenetic, and environmental characteristics. iPSCs, which can be generated from adult cells through reprogramming, offer a remarkable tool for modeling diseases, understanding individual variations, and developing personalized therapies [575]. One of the primary advantages of iPSCs in personalized medicine is their ability to recapitulate the genetic makeup of individual patients [623]. By reprogramming cells from patients with specific diseases or conditions, iPSCs can serve as disease models that accurately reflect the genetic variations present in those patients. This allows researchers to study the underlying mechanisms of diseases at the cellular level and design personalized treatment strategies [622]. Furthermore, iPSCs can be differentiated into various cell types, including those affected by specific diseases. This differentiation potential enables the generation of disease-specific cells, such as cardiomyocytes for heart diseases or neurons for neurodegenerative disorders [568, 575, 584]. By studying these disease-specific cells derived from iPSCs, researchers can gain insights into the molecular changes associated with the disease and identify potential therapeutic targets. In personalized medicine, iPSCs have shown great promise in drug discovery and development [622]. Traditional drug development often relies on animal models or cell lines that may not fully capture the complexity of human diseases. iPSCs, on the other hand, provide a human-specific platform for drug screening and testing. By generating iPSCs from patients with varying responses to specific drugs, researchers can evaluate drug efficacy and toxicity on patient-specific cells [575]. This approach has the potential to optimize drug selection and dosage, leading to improved treatment outcomes and reduced adverse effects. Moreover, iPSCs can be utilized in the field of regenerative medicine, which aims to replace or repair damaged tissues and organs [623]. By differentiating iPSCs into specific cell types, it becomes possible to generate patient-specific cells for transplantation. This approach mitigates the risk of immune rejection, as the transplanted cells are derived from the patient’s own iPSCs. For instance, iPSCs can be differentiated into cardiomyocytes and used for cell-based therapy in patients with heart diseases. This personalized regenerative approach holds immense potential for restoring tissue function and improving patient outcomes [568, 575, 584]. The application of iPSCs in cancer personalized medicine is particularly exciting. Cancer is a highly heterogeneous disease, and treatment response can vary significantly among patients. iPSCs offer the opportunity to generate patient-specific cancer models that closely resemble the individual’s tumor. These models can be used to study the molecular characteristics of the cancer, identify potential therapeutic targets, and predict the response to specific treatments. iPSC-based cancer models also facilitate the screening of anti-cancer drugs, enabling the selection of personalized treatment regimens based on the unique genetic profile of each patient's cancer cells [622]. However, despite the immense potential of iPSCs in personalized medicine, several challenges need to be addressed. The process of reprogramming cells into iPSCs is complex and time-consuming, limiting their immediate clinical application. Additionally, ensuring the safety and efficacy of iPSC-derived cells for transplantation requires rigorous quality control and validation [575]. Moreover, ethical considerations surrounding the generation and use of iPSCs, such as obtaining informed consent and protecting patient privacy, must be carefully addressed to ensure responsible and ethical practices. The iPSCs hold tremendous promise in personalized medicine, offering a unique platform for disease modeling, drug screening, and regenerative therapies [568, 575, 584]. Their ability to recapitulate patient-specific genetic variations and differentiate into disease-specific cells provides valuable insights into individual diseases and facilitates the development of personalized treatment strategies. While challenges exist, continued research and development in iPSC technology, along with the establishment of robust ethical guidelines, will pave the way for the widespread implementation of iPSCs in personalized medicine [623]. To unlock the full potential of iPSCs in personalized medicine, further research is needed to optimize the reprogramming process and improve the efficiency of iPSC generation. Advances in gene-editing technologies, such as CRISPR-Cas9, have the potential to enhance the precision and safety of iPSC reprogramming, making it a more feasible and reliable method for clinical applications [575]. Additionally, efforts should be made to develop standardized protocols for iPSC differentiation into various cell types, ensuring consistency and reproducibility across different laboratories and research settings [622]. Another crucial aspect that requires attention is the establishment of robust bioinformatics and data analysis pipelines to handle the large amount of data generated from iPSC-based personalized medicine studies. Integration of genomics, transcriptomics, proteomics, and other omics data from iPSC-derived cells can provide a comprehensive understanding of disease mechanisms and identify biomarkers for personalized diagnostics and treatment monitoring [623]. The use of iPSCs in personalized medicine holds immense promise for advancing patient care. iPSCs provide a powerful tool for disease modeling, drug screening, and regenerative therapies, enabling a more precise and tailored approach to treatment. While challenges exist, ongoing research and technological advancements, along with collaborative efforts between different stakeholders, will pave the way for the integration of iPSC-based personalized medicine into mainstream healthcare. With continued investment in iPSC research and responsible application, which can harness the full potential of iPSCs to transform the landscape of personalized medicine, offering patients more effective, targeted, and personalized treatment options [568, 575, 584].

The use of iPSCs in cancer early detection and diagnosis

The use of iPSCs in cancer early detection and diagnosis holds immense promise and potential. Cancer is a complex disease characterized by the accumulation of genetic and epigenetic alterations in cells, leading to uncontrolled proliferation and tumor formation [550, 554]. Early detection and accurate diagnosis are crucial for improving patient outcomes and implementing timely and effective treatment strategies [593]. iPSCs, with their unique properties and capabilities, offer a valuable tool in the quest for early cancer detection. iPSCs can be generated by reprogramming adult somatic cells, such as skin cells or blood cells, into a pluripotent state similar to embryonic stem cells. These iPSCs have the ability to differentiate into various cell types, including those found in different organs and tissues affected by cancer [568, 601]. This characteristic makes iPSCs an attractive candidate for modeling cancer initiation and progression. One of the key applications of iPSCs in cancer early detection is the generation of organoids or miniaturized organs in a dish [564, 603]. In a recent investigation led by Hanna et al., the focus was on creating iPSCs that closely resembled mouse embryonic stem cells (mESCs) in terms of their biological and epigenetic characteristics [628]. The study centered on employing a novel reprogramming approach to transform hESCs into a less mature state resembling mESCs. Figure 11 provides a visual representation of the iPSC generation process using this method. By inducing the expression of Oct4, Klf4, and Klf2 factors in hESCs and subjecting them to specific growth conditions, the researchers successfully generated what they referred to as “epigenetically converted cells.” These cells exhibited striking similarities to mESCs in terms of growth properties, gene expression patterns, and reliance on specific signaling pathways, as highlighted in Fig. 11. Additionally, Fig. 11 underscores the likenesses between naive hESCs and mESCs in signaling and epigenetic characteristics. Figure 11 further demonstrates the connection between naive hESCs, hiPSCs, and mESCs based on their transcriptional profiles, showcasing the success of the reprogramming approach in producing hiPSCs that closely mimic mESCs. These findings pave the way for a deeper understanding of pluripotency in humans and hold great promise for conducting disease-specific research using patient-derived iPSCs. The iPSCs can be directed to differentiate into specific cell types relevant to different cancer types, allowing the creation of organoids that closely mimic the structure and function of actual organs [556]. These organoids can be used to study the early stages of cancer development, providing researchers with a platform to investigate the molecular changes and cellular interactions that drive tumor formation. Furthermore, iPSC-derived organoids can be utilized for personalized medicine approaches in cancer diagnosis [130, 577, 629]. By obtaining patient-derived iPSCs, researchers can generate organoids that replicate the genetic and epigenetic makeup of the individual's tumor. This personalized organoid model can then be used to test the efficacy of different treatment options, helping clinicians identify the most effective therapeutic strategies for specific patients [630, 631]. This approach holds the potential to optimize treatment outcomes by tailoring therapies to the individual characteristics of each patient's cancer. In addition to organoid models, iPSCs can also be employed for the development of non-invasive diagnostic tools for cancer. Traditional cancer diagnostic methods often involve invasive procedures such as biopsies, which can be uncomfortable for patients and may carry associated risks. iPSCs offer a non-invasive alternative by allowing the generation of liquid biopsy models [376, 610]. iPSC-derived cells can be released into the bloodstream and collected for analysis, providing valuable information about the presence and characteristics of tumors [610]. Liquid biopsy-based approaches using iPSCs have the potential to revolutionize cancer diagnosis, enabling early detection and monitoring of disease progression in a minimally invasive manner [632]. Moreover, iPSCs can be genetically modified to express specific reporter genes or markers that are associated with cancer. These modified iPSCs can be used to develop sensitive and specific biosensors for the detection of cancer-related molecules or biomarkers in patient samples. By leveraging the unique properties of iPSCs, such as their ability to self-renew and differentiate, these biosensors can provide highly accurate and reliable diagnostic information [633, 634]. Despite the tremendous potential of iPSCs in cancer early detection and diagnosis, there are challenges that need to be addressed. One such challenge is the efficient and standardized generation of iPSCs from patient samples [490, 635]. The reprogramming process can be time-consuming and may require optimization to ensure the generation of high-quality iPSCs [636]. Additionally, the scalability of iPSC-based diagnostic approaches needs to be improved to enable their widespread clinical implementation [637]. Ethical and legal considerations also come into play when using iPSCs for cancer research and diagnosis. Ensuring informed consent and protecting patient privacy are paramount. Guidelines and regulations should be established to govern the collection, storage, and use of patient-derived iPSCs for diagnostic purposes, ensuring that ethical standards are upheld and patient rights are respected [557, 572]. The use of iPSCs in cancer early detection and diagnosis represents a promising avenue of research [623]. iPSC-derived organoids and liquid biopsy models offer tremendous potential in understanding the molecular mechanisms underlying cancer initiation and progression. These models can help identify key genetic and epigenetic alterations associated with specific cancer types, enabling the development of targeted therapies tailored to individual patients [633, 634]. Furthermore, iPSC-based diagnostic tools, such as biosensors and liquid biopsy approaches, hold the promise of non-invasive and highly sensitive detection of cancer-related molecules and biomarkers. These innovative techniques have the potential to revolutionize cancer diagnosis by providing early detection, monitoring disease progression, and assessing treatment response in a minimally invasive manner [630, 631]. By avoiding the need for invasive procedures like biopsies, iPSC-based diagnostics can significantly improve patient comfort and reduce associated risks. Moreover, iPSCs can be used in conjunction with other diagnostic modalities, such as imaging techniques, to enhance the accuracy and reliability of cancer diagnosis. Combining iPSC-based models with imaging technologies allows for a comprehensive analysis of tumor characteristics, including size, location, and molecular features [633, 634]. This integrative approach can provide clinicians with a more comprehensive understanding of the disease, aiding in the selection of appropriate treatment strategies [630, 631]. Despite the remarkable potential of iPSCs in cancer early detection and diagnosis, several challenges need to be overcome before their widespread clinical implementation. Standardizing the generation of iPSCs and optimizing the differentiation protocols to produce organoids that faithfully recapitulate the complexity of real tumors are essential steps. Additionally, large-scale validation studies are necessary to assess the sensitivity, specificity, and reliability of iPSC-based diagnostic approaches across different cancer types and patient populations [630, 631]. Furthermore, regulatory frameworks and guidelines should be established to address the ethical and legal considerations associated with iPSC research [633, 634]. Ensuring informed consent, protecting patient privacy, and adhering to ethical standards are paramount when utilizing iPSCs in cancer research and diagnostics. Collaboration between researchers, clinicians, ethicists, and regulatory authorities is crucial to develop guidelines that safeguard patient rights and promote responsible and ethical use of iPSCs [610]. The iPSCs offer a promising avenue for early cancer detection and diagnosis. Their ability to generate organoids, develop biosensors, and serve as liquid biopsies opens up new possibilities for understanding the molecular basis of cancer and implementing personalized treatment strategies. While there are challenges to overcome, continued investment in iPSC research and collaborative efforts among stakeholders can pave the way for the clinical translation of iPSC-based approaches, ultimately leading to improved cancer outcomes and patient care [633, 634].

Future of iPSCs in tumorigenesis

The future of iPSCs in tumorigenesis holds great promise, offering opportunities for advancements in precision medicine, the development of new therapies, the creation of more advanced models for research, and integration with other emerging technologies [549, 556, 638]. The future of iPSCs in tumorigenesis research is extremely promising. iPSCs have the potential to advance precision medicine by providing patient-specific models for personalized therapies and enabling the identification of specific genetic and epigenetic alterations associated with cancer [576]. The development of new cancer therapies is also within reach, as iPSCs can be utilized for drug screening, gene therapy, and the production of immune cells with enhanced anti-tumor properties [551, 555, 584, 596]. However, further advancements are needed in the development of more advanced iPSC models that accurately mimic the complex tumor microenvironments and facilitate the study of tumor heterogeneity and therapeutic resistance. Integrating iPSCs with other emerging technologies, such as gene editing, single-cell sequencing, and bioengineering, will further enhance our understanding of tumorigenesis and aid in the identification of novel biomarkers and therapeutic targets [130, 629, 639]. The continued investment in iPSC research, along with collaborations between scientists and clinicians, will be crucial in unlocking the full potential of iPSCs in tumorigenesis and therapy. The future of iPSCs in tumorigenesis research is bright, offering exciting prospects for precision medicine, the development of innovative therapies, advanced models for research, and integration with other cutting-edge technologies. As scientists continue to explore the vast potential of iPSCs, we can look forward to groundbreaking discoveries that will shape the field of cancer research and ultimately improve patient outcomes.

iPSCs have the potential to revolutionize cancer precision medicine

These cells can be generated from patients' own somatic cells, allowing for the creation of patient-specific iPSC lines [612, 640]. This opens up avenues for personalized medicine approaches in cancer treatment (Table 9). By deriving iPSCs from cancer patients, researchers can study the molecular changes that occur during tumorigenesis and identify specific genetic and epigenetic alterations associated with the disease [15, 24]. iPSCs can be differentiated into various cell types, including cancer cells, which enables the development of personalized therapies targeting the specific cancer subtypes present in individual patients [24]. The use of iPSCs in precision medicine holds the promise of tailoring treatments to individual patients based 9.2.

iPSCs offer the potential to develop new cancer therapies

Through iPSC-based technologies, researchers can generate large quantities of patient-specific cells, including cancer cells, which can be used for drug screening and testing [584]. This allows for the identification of novel compounds or combinations of drugs that are more effective in targeting cancer cells while minimizing the toxicity on healthy tissues [585, 626]. iPSCs can also be genetically engineered to correct cancer-associated mutations or introduce therapeutic genes, providing a platform for gene therapy approaches [555]. Additionally, iPSCs can be utilized to produce immune cells with enhanced anti-tumor properties, facilitating the development of immunotherapies for cancer treatment. The versatility and adaptability of iPSCs make them a valuable tool in the development of innovative cancer therapies [551, 583, 599].

Table 9 The transformative role of iPSCs in advancing cancer precision medicine

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iPSCs offer the potential to develop new cancer therapies

Through iPSC-based technologies, researchers can generate large quantities of patient-specific cells, including cancer cells, which can be used for drug screening and testing [610]. This allows for the identification of novel compounds or combinations of drugs that are more effective in targeting cancer cells while minimizing the toxicity on healthy tissues. iPSCs can also be genetically engineered to correct cancer-associated mutations or introduce therapeutic genes, providing a platform for gene therapy approaches [542]. Additionally, iPSCs can be utilized to produce immune cells with enhanced anti-tumor properties, facilitating the development of immunotherapies for cancer treatment. The versatility and adaptability of iPSCs make them a valuable tool in the development of innovative cancer therapies [555, 606].

The development of more advanced iPSC models for tumorigenesis research is a crucial area of focus

Current iPSC models provide valuable insights into the early stages of cancer development and progression. However, there is a need for more sophisticated models that accurately recapitulate the complex dynamics of tumor microenvironments, including interactions with stromal cells, immune cells, and extracellular matrices. Advances in tissue engineering and organoid technology are being integrated with iPSCs to create 3D tumor models that better mimic the physiological conditions of tumors in vivo [324]. These advanced models can enhance our understanding of tumor heterogeneity, therapeutic resistance, and metastasis, enabling the development of more effective treatment strategies [125]. Furthermore, the integration of patient-derived iPSCs with advanced genomic and proteomic analyses can provide comprehensive molecular characterization of tumors, aiding in the identification of novel biomarkers and therapeutic targets [641, 642].

The integration of iPSCs with other emerging technologies in cancer research holds significant potential

iPSCs can be combined with gene editing techniques, such as CRISPR-Cas9, to introduce precise genetic modifications or perform functional genomics studies to elucidate the role of specific genes in tumorigenesis [606, 638, 643]. Moreover, the integration of iPSCs with single-cell sequencing technologies allows for the analysis of individual cancer cells, revealing heterogeneity and clonal evolution within tumors [639]. This information can guide treatment decisions and identify novel targets for therapy. Furthermore, the integration of iPSCs with bioengineering approaches, such as microfluidics and organ-on-a-chip systems, enables the study of tumor cell migration, invasion, and response to therapeutic agents in more physiologically relevant environments [540]. By combining iPSCs with these emerging technologies, researchers can gain deeper insights into the mechanisms underlying tumorigenesis and develop innovative strategies for cancer diagnosis and treatment. Table 10 provides an insightful overview of emerging technologies in iPSC-based cancer research.

Table 10 An overview of the emerging technologies in iPSC-based cancer research

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Case studies

The case studies mentioned emphasize the successful use of iPSCs in studying the development of cancer and their significant impact on the advancement of cancer therapies. iPSCs provide unique opportunities in various areas, including modeling diseases [15], tailoring treatments, screening drugs [556], regenerative medicine [125], immunotherapies [608], early cancer detection, and precision medicine [24]. By serving as a platform to investigate the complex mechanisms involved in cancer development, iPSCs have expanded our knowledge of the genetic, epigenetic, and environmental factors contributing to cancer [545]. Furthermore, iPSCs have played a vital role in developing individualized and targeted therapies, offering great potential for improving patient outcomes and reducing the overall burden of cancer [531]. As research progresses in the field of iPSCs and tumorigenesis, it is important to address the challenges and limitations associated with iPSC-based approaches. This includes enhancing the efficiency of iPSC generation, refining differentiation protocols to generate specific cell types more effectively, and considering the ethical and regulatory aspects of iPSC research [545]. Continued investment in iPSC research and fostering collaboration among scientists, clinicians, and policymakers will further unlock the full potential of iPSCs in cancer research and therapy development. This collaborative effort holds the promise of devising better strategies for cancer prevention, early detection, and personalized treatment approaches that can greatly impact the field of oncology. Table 11 highlights several significant case studies in cancer research that have utilized iPSCs.

Table 11 Significant iPSC-based cancer research case studies

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iPSC-based disease modeling

Disease modeling involves generating in vitro models of human diseases to understand the underlying mechanisms, test drug efficacy, and develop new treatments. Traditionally, disease modeling relied on animal models or immortalized cell lines, both of which have limitations in recapitulating human disease due to differences in physiology, genetic makeup, and epigenetic regulation [553]. In a recent study, some researchers provided the remarkable potential of human induced pluripotent stem (iPS) cells for disease modeling was highlighted [726]. The researchers utilized iPS cells to model both cardiac and neural diseases, as depicted in Fig. 12 of their study. By reprogramming somatic cells from patients with these diseases, they were able to generate patient-specific iPS cells, which accurately recapitulated disease phenotypes in vitro. This breakthrough allowed for a deeper understanding of the underlying mechanisms and pathophysiology of these diseases. Additionally, Fig. 12 in the study illustrated the process of deriving and utilizing iPS cells, emphasizing their pivotal role in advancing regenerative medicine and drug discovery. The findings from this study underscore the immense potential of iPS cells in revolutionizing disease research and personalized medicine. The iPSCs offer several advantages over traditional disease models. Firstly, iPSCs can be derived directly from patients with a disease, allowing for the modeling of patient-specific diseases [543]. This is particularly relevant for diseases with a strong genetic component, such as cancer, where different mutations in the same gene can result in different cancer subtypes and response to treatment [543]. Secondly, iPSCs can be differentiated into different cell types, including disease-relevant cell types, such as neurons for neurodegenerative diseases, cardiomyocytes for cardiovascular diseases, and hepatocytes for liver diseases [247, 727]. This enables the generation of more physiologically relevant disease models that mimic the tissue-specific characteristics of the disease [543]. Lastly, iPSC-based disease models can be used to test drug efficacy and toxicity, potentially leading to the development of more effective and safer treatments [125, 626]. In a recent study conducted by Lowry et al., the researchers focused on generating human induced pluripotent stem (iPS) cells from dermal fibroblasts, with the aim of advancing stem cell-based therapies for degenerative diseases [728]. In a recent investigation led by Lowry and colleagues, the primary focus was on the generation of iPS cells from dermal fibroblasts, aiming to advance the use of stem cell-based therapies for degenerative diseases [728]. The study employed specific transcription factors, including KLF4, OCT4, SOX2, and C-MYC, to reprogram dermal fibroblasts into iPS cells. The outcomes, illustrated in Fig. 13, indicated a striking resemblance of the iPS cell clones to human embryonic stem cells (HESC) in terms of their visual characteristics. Furthermore, Fig. 13 presented evidence that these iPS clones expressed key markers typically associated with HESC, suggesting a molecular similarity. Transcriptome analysis, as shown in Fig. 13, further affirmed the likeness in gene expression profiles between iPS clones and HESC. Additionally, Fig. 13 provided evidence that iPS cells could form embryoid bodies (EBs) akin to HESC, and Fig. 13 emphasized the pluripotent nature of iPS cells by demonstrating their capacity to differentiate into ectoderm, endoderm, and mesoderm lineages. These findings underscore the pivotal role of iPSCs in offering an abundant source of patient-specific pluripotent stem cells with potential clinical applications.

Case study: iPSC-based modeling of Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a rare hereditary disease characterized by the development of multiple adenomatous polyps in the colon and rectum, leading to a high risk of colon cancer. FAP is caused by mutations in the adenomatous polyposis coli (APC) gene, which regulates cell proliferation and differentiation. However, the molecular mechanisms underlying the development of FAP and the progression to colon cancer are not fully understood. In a recent study, iPSCs were generated from skin fibroblasts of FAP patients with different APC mutations and differentiated into intestinal organoids, which mimic the structure and function of the intestinal epithelium. The iPSC-derived organoids from FAP patients showed an increased number of polyps, aberrant Wnt signaling pathway activation, and increased proliferation compared to healthy control organoids. These results suggest that APC mutations lead to increased proliferation and aberrant Wnt signaling in the intestinal epithelium, contributing to the development of FAP and colon cancer. Furthermore, the FAP patient-derived organoids were sensitive to a Wnt inhibitor, demonstrating the potential of using iPSC-based disease models for drug discovery and personalized medicine [729].

Impact on tumorigenesis understanding

Tumorigenesis is a complex process involving multiple genetic and epigenetic alterations that drive normal cells to become cancerous. Understanding the molecular mechanisms underlying tumorigenesis is critical for developing new cancer therapies and improving patient outcomes [530, 730]. iPSC-based disease modeling provides a powerful tool for studying tumorigenesis, as it allows for the generation of patient-specific disease models that recapitulate the tissue-specific characteristics of the cancer [730]. The iPSC-based disease models have been used to study the molecular changes associated with tumorigenesis, including changes in gene expression, epigenetic modifications, and protein signaling pathways [729]. For example, iPSC-based disease models have been used to study the genetic and epigenetic alterations associated with the development of breast cancer, leukemia, and glioblastoma [533, 549, 627]. These studies have provided valuable insights into the early events of cancer development and the underlying molecular mechanisms. In the context of tumorigenesis, iPSC-based disease models have helped uncover key genes and signaling pathways involved in tumor initiation and progression [543, 730]. By comparing iPSCs derived from healthy individuals and those with cancer, researchers have identified genetic mutations and gene expression changes specific to cancer cells. These findings have shed light on the dysregulation of important cellular processes, such as cell cycle control, DNA repair mechanisms, and cell signaling pathways, contributing to the understanding of how normal cells transform into cancer cells [24]. Furthermore, iPSC-based disease models have been instrumental in elucidating the role of epigenetic modifications in tumorigenesis. Epigenetic alterations, such as DNA methylation and histone modifications, can regulate gene expression patterns and contribute to the development and progression of cancer. iPSCs derived from cancer patients have allowed researchers to investigate epigenetic changes associated with specific cancer types and identify potential epigenetic markers for early cancer detection and targeted therapies [24]. Importantly, iPSC-based disease models have facilitated the study of tumor heterogeneity, a hallmark of cancer, which refers to the genetic and phenotypic diversity observed within tumors. By generating iPSCs from different regions or subpopulations of tumors, researchers have been able to recreate the heterogeneous nature of cancers in vitro [730]. This has enabled the exploration of tumor evolution, clonal dynamics, and the identification of subpopulations of cells responsible for metastasis or resistance to therapy [576]. Such knowledge is invaluable for developing personalized treatment strategies tailored to individual patients. Table 12 presents an overview of key case studies highlighting the application of iPSCs in understanding tumorigenesis.

Table 12 Key iPSC-based tumorigenesis case studies

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Personalized medicine and drug screening

Personalized medicine and drug screening are two interconnected concepts that have the potential to revolutionize healthcare [15]. Personalized medicine aims to tailor medical treatment to an individual's unique genetic makeup, lifestyle, and environmental factors [731]. Drug screening, on the other hand, involves testing a large number of compounds to identify potential drug candidates for a specific disease or condition [15]. Personalized medicine is based on the premise that every individual is unique and responds differently to medical treatments. The use of genomic sequencing, proteomic profiling, and other advanced technologies has made it possible to identify specific genetic mutations and biomarkers associated with different diseases [732]. By analyzing an individual's genetic makeup, physicians can identify which drugs are likely to be most effective and which ones may cause harmful side effects. One example of personalized medicine is the use of targeted therapies for cancer treatment [733]. Traditional chemotherapy drugs kill rapidly dividing cells, including healthy cells, leading to many negative side effects. Targeted therapies, however, are designed to specifically target cancer cells by exploiting their genetic vulnerabilities. For instance, some cancer cells have overactive growth receptors on their surface, which targeted therapies can block, slowing down cancer growth. Drug screening is a crucial step in the drug development process. It involves testing thousands of compounds to identify those that have the potential to become effective drugs for a specific disease or condition [611]. High-throughput screening (HTS) is a popular approach that allows researchers to rapidly test a large number of compounds. HTS can be used to identify new drugs, repurpose existing drugs for new uses, or optimize existing drugs to improve their efficacy [731]. Advances in drug screening technologies, such as computer simulations and artificial intelligence (AI), have significantly accelerated the drug discovery process. These technologies can predict how a drug will interact with a specific target, predict toxicity, and identify potential drug combinations [732]. By using these tools, researchers can quickly identify potential drug candidates and prioritize those with the greatest potential for success. Personalized medicine and drug screening are becoming increasingly intertwined [15]. By analyzing an individual's genetic makeup, physicians can identify which drugs are likely to be most effective for a particular patient. This can significantly reduce the trial-and-error process associated with traditional medicine [732]. Drug screening can also be personalized by testing drugs on patient-derived cells or tissue samples. This approach can help predict which drugs are most likely to be effective for a particular patient, and avoid those that are likely to cause harm [733]. One example of the integration of personalized medicine and drug screening is the development of immunotherapies for cancer treatment [731]. Immunotherapies work by stimulating the body's immune system to target and kill cancer cells. However, not all patients respond equally to immunotherapies [733]. By analyzing an individual's genetic makeup, researchers can identify which patients are most likely to respond to a particular immunotherapy and which ones are not. This can help tailor treatment to each patient and improve the overall success rate of immunotherapies. Personalized medicine and drug screening are two important concepts that have the potential to transform healthcare [15]. Personalized medicine aims to tailor medical treatment to an individual's unique genetic makeup, lifestyle, and environmental factors, while drug screening involves testing a large number of compounds to identify potential drug candidates for a specific disease or condition [732]. The integration of these two concepts can significantly improve patient outcomes by reducing trial and error and tailoring treatment to each individual's needs. With advances in technology and research, personalized medicine and drug screening are poised to become the standard of care in many areas of healthcare [733].

Regenerative medicine and immunotherapies

Regenerative medicine and immunotherapies represent groundbreaking approaches in the field of healthcare, offering promising solutions for the treatment of various diseases, including cancer [555, 606]. Regenerative medicine aims to restore, replace, or regenerate damaged tissues and organs, while immunotherapies harness the power of the immune system to combat diseases. These two fields have gained significant attention and are revolutionizing the landscape of modern medicine [731]. Regenerative medicine focuses on harnessing the regenerative potential of stem cells, including iPSCs, to repair and replace damaged tissues and organs [732]. iPSCs are generated by reprogramming adult cells, such as skin cells, into a pluripotent state, giving them the ability to differentiate into various cell types. This remarkable feature of iPSCs makes them an attractive tool for regenerative medicine applications [611]. They can be differentiated into specific cell lineages, such as cardiomyocytes for heart repair or pancreatic beta cells for diabetes treatment [15]. One of the key advantages of regenerative medicine is its potential to provide personalized therapies. By utilizing a patient's own cells to generate iPSCs, it becomes possible to create tissue or organ grafts that are genetically identical to the patient, reducing the risk of immune rejection and the need for immunosuppressive drugs. This personalized approach holds great promise for improving patient outcomes and minimizing complications associated with traditional transplantation methods. In the realm of cancer treatment, regenerative medicine offers innovative strategies. iPSCs can be used to model cancer in a laboratory setting, providing researchers with a platform to study the mechanisms of tumor formation, progression, and response to various treatments. This enables the development of more effective and targeted therapies [555, 606]. Furthermore, iPSCs can be engineered to express therapeutic genes or anti-cancer agents, acting as “cellular factories” that produce and release these substances specifically at the site of the tumor. Immunotherapies, on the other hand, harness the body's immune system to recognize and eliminate cancer cells. Traditional cancer treatments, such as chemotherapy and radiation therapy, often have systemic side effects and can harm healthy tissues [15]. Immunotherapies offer a more targeted approach, aiming to enhance the immune response against cancer cells while minimizing damage to normal cells [732]. One of the most exciting developments in immunotherapy is the use of immune checkpoint inhibitors [611]. These inhibitors block the proteins that prevent immune cells from recognizing and attacking cancer cells. By releasing these immune checkpoints, the body's immune system is reactivated and can mount a robust response against the tumor. This approach has shown remarkable success in treating various cancers, including melanoma, lung cancer, and bladder cancer [555, 606]. Another promising immunotherapy strategy is adoptive cell transfer, which involves isolating immune cells, such as T cells, from a patient, genetically modifying them to express receptors that recognize specific cancer antigens, and then reintroducing these cells back into the patient's body [732]. These modified immune cells can then specifically target and eliminate cancer cells, leading to tumor regression. This approach has shown remarkable efficacy in the treatment of hematological malignancies, such as leukemia and lymphoma. Combining regenerative medicine with immunotherapies can offer even greater therapeutic potential [555, 606]. iPSCs can be genetically engineered to express immune-stimulatory molecules, such as cytokines, which can enhance the immune response against tumors [15]. Furthermore, iPSCs can be differentiated into immune cells, such as dendritic cells or natural killer cells, which can be used in cancer immunotherapies to enhance the anti-tumor immune response. Regenerative medicine and immunotherapies are revolutionizing the field of healthcare, particularly in the realm of cancer treatment. The regenerative potential of iPSCs opens up new avenues for tissue repair and personalized therapies [611]. Meanwhile, immunotherapies are providing targeted and effective approaches to activate the immune system against cancer cells. Combining these two fields can lead to even more effective and personalized treatments for patients [731]. However, as with any emerging technology, there are also challenges and ethical considerations that need to be addressed. One of the key challenges is the safety and efficacy of these therapies [732]. While regenerative medicine and immunotherapies hold great promise, more research is needed to fully understand their mechanisms and potential risks. There is also a need for standardized protocols for the manufacturing, testing, and administration of these therapies to ensure their safety and efficacy. Another consideration is the cost and accessibility of these therapies [611]. Regenerative medicine and immunotherapies can be expensive, and there is a need to ensure that they are accessible to all patients who could benefit from them. This includes developing more affordable and scalable manufacturing methods for these therapies [15]. There are also ethical considerations related to the use of human embryonic stem cells and iPSCs. While the use of iPSCs avoids the ethical concerns associated with the use of embryonic stem cells, there are still concerns regarding the consent and privacy of patients who donate their cells for research [555, 606]. There is a need for clear guidelines and ethical frameworks to ensure that the use of iPSCs is conducted in an ethical and responsible manner. Despite these challenges, regenerative medicine and immunotherapies represent a promising future for healthcare [611]. By harnessing the regenerative potential of stem cells and the power of the immune system, these therapies offer innovative solutions for the treatment of various diseases, including cancer. With continued research and development, regenerative medicine and immunotherapies have the potential to transform the way we approach healthcare and provide personalized and effective treatments for patients. In addition to their potential in cancer treatment, regenerative medicine and immunotherapies hold promise in a wide range of other medical conditions [732]. For example, in the field of tissue engineering, regenerative medicine approaches aim to create functional tissues and organs that can replace damaged or diseased ones. This can be particularly beneficial for patients with organ failure or those in need of organ transplantation. By utilizing stem cells and bioengineering techniques, researchers are making strides in developing functional tissues such as heart muscle, liver tissue, and even entire organs like kidneys [15]. Furthermore, regenerative medicine approaches are being explored for the treatment of degenerative diseases such as Parkinson's and Alzheimer's. The ability to generate specific cell types from stem cells opens up possibilities for cell replacement therapies. Scientists are investigating the use of iPSCs to generate neurons that can be transplanted into the brains of patients with neurodegenerative disorders, potentially restoring lost function and improving quality of life [732]. Immunotherapies, on the other hand, have shown promise in various other areas beyond cancer treatment [611]. For instance, they are being investigated for the treatment of autoimmune diseases, where the immune system mistakenly attacks healthy cells and tissues. By modulating the immune response, immunotherapies offer a targeted approach to suppress or regulate the immune system, reducing inflammation and preventing damage to the body's own tissues. Moreover, immunotherapies have demonstrated potential in infectious diseases, such as HIV and viral hepatitis [555, 606]. Researchers are exploring strategies to boost the immune system's ability to recognize and eliminate viral pathogens, offering new avenues for the development of antiviral therapies [611]. In the field of transplantation, immunotherapies are being investigated to improve the success of organ and tissue transplantation. By modulating the immune response and preventing organ rejection, these therapies have the potential to increase the availability of donor organs and improve patient outcomes [732]. While regenerative medicine and immunotherapies are still relatively new fields, the progress and advancements made so far are highly promising [733]. Ongoing research and clinical trials are expanding our understanding of these approaches and paving the way for their integration into mainstream medical practice [611]. Regenerative medicine and immunotherapies represent transformative approaches in healthcare, with the potential to revolutionize the treatment of various diseases. Regenerative medicine offers the possibility of tissue and organ regeneration, personalized therapies, and disease modeling using iPSCs. Immunotherapies harness the power of the immune system to target and eliminate cancer cells, as well as to treat autoimmune disorders and infectious diseases [555, 606]. In a recent study conducted by Wang et al., the researchers investigated the immunogenicity and functional evaluation of iPSC-derived organs for transplantation [734]. The study aimed to determine whether iPSC-derived organs, including skin, islet, and heart tissues, were capable of surviving, repairing tissue damage, and functioning effectively after transplantation. The researchers utilized 4n complementation to generate iPSC-derived organs without integration. Figure 14 highlights the process of creating 4n complementation mice using iPSCs without integration, showcasing the innovative approach employed in this study. Figure 14 demonstrates the successful transplantation of iPSC-derived skin, which not only survived but also effectively repaired skin wounds in recipient mice. This finding indicates the potential therapeutic application of iPSC-derived skin for tissue regeneration. Figure 14 further illustrates the positive effects of iPSC-derived islets in diabetic mouse models. The transplanted iPSC-derived islets successfully produced insulin and effectively reduced high glucose levels, suggesting their therapeutic potential for treating diabetes. Importantly, Fig. 14 also highlights the limited immunogenicity of iPSC-derived islets, indicating their compatibility for transplantation without eliciting significant immune rejection responses. In Fig. 14, the outcomes of heart transplantation using iPSC-derived hearts are depicted. The iPSC-derived heart grafts displayed normal beating for a duration of over 3 months in syngeneic recipients, demonstrating their functional viability and long-term survival. This finding provides promising evidence for the feasibility of using iPSC-derived hearts in transplantation procedures. In a recent investigation conducted by Wang and colleagues, the researchers explored the immune response and functional assessment of organs derived from iPSCs intended for transplantation [734]. The study aimed to ascertain whether iPSC-derived organs, such as skin, islet, and heart tissues, could endure, repair damaged tissue, and operate effectively post-transplantation. To create iPSC-derived organs devoid of integration, the researchers employed a 4n complementation approach. Figure 14 illustrates the process of generating 4n complementation mice using iPSCs without integration, showcasing the innovative method used. Figure 14 showcases the successful transplantation of iPSC-derived skin, which not only survived but also efficiently healed skin injuries in recipient mice, suggesting the potential therapeutic utility of iPSC-derived skin for tissue regeneration. Figure 14 further illustrates the favorable effects of iPSC-derived islets in diabetic mouse models. These transplanted islets produced insulin and effectively lowered elevated glucose levels, indicating their potential for treating diabetes. Additionally, Fig. 14 highlights the limited immunogenicity of iPSC-derived islets, suggesting their compatibility for transplantation without significant immune rejection. In Fig. 14, the results of heart transplantation using iPSC-derived hearts are depicted. The iPSC-derived heart grafts exhibited normal beating for over 3 months in syngeneic recipients, demonstrating their functional viability and long-term survival. This discovery offers promising evidence for the practicality of utilizing iPSC-derived hearts in transplantation procedures.

Ethical and legal considerations

In recent years, the iPSCs have emerged as a powerful tool in cancer research and therapy [41, 735]. However, their use raises important ethical and legal considerations that need to be carefully addressed. This section will discuss four key aspects: the ethics of using human cells in iPSC research, intellectual property rights, regulation of iPSC research, and the need for international consensus on ethical and legal issues [15, 736]. The utilization of human cells, including iPSCs, raises ethical questions related to the source of cells, their derivation, and potential risks [45, 737]. iPSCs are typically generated from adult somatic cells, such as skin or blood cells, which are reprogrammed to exhibit pluripotent properties [41, 738]. While these cells offer great potential for advancing cancer research, their use necessitates ethical considerations. Researchers must ensure that individuals providing cells for iPSC research are adequately informed about the purpose, risks, and potential benefits of the research [38, 739]. Respect for donor autonomy and privacy should be maintained throughout the process, including secure data management and confidentiality. Another ethical consideration is the use of embryos in iPSC research. Initially, iPSCs were generated by reprogramming human embryos, which raised ethical concerns due to the destruction of embryos [41, 740]. However, advancements in reprogramming techniques now allow for the generation of iPSCs from adult cells, avoiding the need for embryo destruction. This approach alleviates ethical concerns associated with embryo use [15, 741]. Intellectual property rights play a significant role in iPSC research, as they can impact the accessibility and affordability of iPSC-based cancer therapies. Patents are often filed for specific techniques, methods, or applications involving iPSCs [45]. These patents grant exclusive rights to the patent holder, potentially limiting the development of alternative therapies. The issue of patenting iPSC technology raises concerns about equitable access to treatments and the sharing of scientific knowledge [41, 742]. Balancing the interests of patent holders with the broader goal of advancing cancer research and treatment is crucial [15]. Encouraging collaborations, licensing agreements, and patent pools can foster innovation while ensuring that iPSC technology is accessible to all researchers and clinicians. Regulation is an essential aspect of iPSC research to ensure the safety and ethical conduct of experiments [45, 743]. Regulatory frameworks differ among countries, and variations in regulations can impact the pace of progress in iPSC-based cancer research. Stringent regulations may slow down research by imposing lengthy approval processes and stringent safety requirements [41, 744]. While necessary to protect participants and patients, these regulations should be designed to strike a balance between safety and facilitating scientific advancements. Harmonizing regulatory standards across countries can promote collaboration, knowledge sharing, and the efficient translation of iPSC-based therapies from the lab to the clinic. Given the global nature of scientific research and the potential impact of iPSCs on tumorigenesis and therapy, there is a pressing need for international consensus on ethical and legal issues [15]. Establishing guidelines and standards can ensure uniformity in research practices and promote responsible and ethical use of iPSCs [38, 745]. International consensus can address several aspects, including informed consent procedures, data sharing, privacy protection, and research collaborations [45, 746]. By facilitating dialogue and agreement among researchers, clinicians, ethicists, and policymakers from different countries, international consensus can help navigate the ethical complexities associated with iPSC research [41, 747]. Collaborative efforts such as the International Society for Stem Cell Research (ISSCR) and national regulatory bodies play a vital role in fostering consensus and developing guidelines. These initiatives promote transparency, encourage ethical conduct, and address the legal challenges surrounding iPSC research [45, 748]. Through international collaboration, stakeholders can share best practices, exchange knowledge, and establish common ethical standards. This can enhance the credibility and reliability of iPSC-based cancer research and ensure that the potential benefits are maximized while minimizing potential risks [41, 749]. Moreover, international consensus on intellectual property rights can facilitate the fair and equitable distribution of iPSC technologies. It can encourage licensing agreements that allow for broader access to iPSC-related discoveries, thereby promoting innovation and accelerating progress in cancer research [15, 750]. Addressing ethical and legal considerations surrounding iPSC research requires interdisciplinary engagement. Collaboration between scientists, clinicians, ethicists, legal experts, policymakers, and patient advocacy groups is crucial to develop comprehensive guidelines that navigate the complex ethical landscape [45, 751]. Furthermore, public engagement and dialogue are vital to ensure that societal values and concerns are taken into account. Including diverse perspectives and involving the public in discussions related to iPSC research can foster transparency, trust, and support for scientific endeavors [38, 752]. As with any emerging technology, safety is a paramount concern in iPSC research. It is essential to thoroughly assess the potential risks associated with the use of iPSCs, such as tumorigenicity, genetic instability, and immunogenicity [15, 753,754,755,756,757,758]. Robust preclinical studies and careful monitoring of patients participating in clinical trials are crucial to ensure the safety and efficacy of iPSC-based therapies. Respecting patient autonomy and ensuring informed consent are central to conducting ethical iPSC research. Patients must have a clear understanding of the nature of the research, potential benefits and risks, and their rights to withdraw from participation at any time [41, 759]. Informed consent processes should be transparent, comprehensive, and culturally sensitive, taking into account the unique challenges and complexities of iPSC research [45, 760]. The development of iPSC-based therapies has the potential to revolutionize cancer treatment, but it is important to ensure that the benefits are accessible and affordable for all patients [38, 761,762,763]. Addressing issues of affordability, equitable distribution, and fair pricing can help mitigate disparities in access to these advanced therapies [38, 764,765,766,767,768]. Collaboration between researchers, industry, and policymakers is vital in developing strategies to make iPSC-based treatments accessible to diverse populations. Public perception and understanding of iPSC research can greatly influence its acceptance and support. Public education initiatives aimed at increasing awareness and knowledge about iPSCs, their potential applications, and the ethical considerations involved are essential [41, 769]. Open dialogue between scientists and the public can foster trust, address concerns, and ensure that societal values are reflected in the development and implementation of iPSC-based therapies. As iPSC-based therapies move from research settings to clinical applications, long-term monitoring and follow-up of patients are crucial [15, 770]. This is necessary to assess the long-term safety, effectiveness, and potential side effects of iPSC-based treatments [38, 771]. Establishing comprehensive surveillance programs and patient registries can provide valuable data for ongoing evaluation and refinement of iPSC therapies [45, 772]. Effective ethical oversight and governance mechanisms are essential to ensure the responsible conduct of iPSC research. Regulatory bodies, research institutions, and ethics committees play a vital role in reviewing and approving research protocols, monitoring compliance with ethical guidelines, and addressing any ethical concerns that may arise [38, 773]. Table 13 highlights the key ethical and legal considerations associated with iPSC research. These considerations play a crucial role in shaping the ethical framework and legal regulations surrounding the field. They encompass various aspects such as informed consent, privacy protection, research involving human subjects, intellectual property rights, and potential misuse of iPSC technology.

Table 13 Key ethical and legal considerations in iPSC research

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Unveiling the potential and challenges of iPSCs in cancer initiation research

In the field of cancer research, gaining a deep understanding of the complexities involved in the initiation of cancer is a crucial and top-priority objective [15]. One groundbreaking approach that has significantly transformed our methods for deciphering this mysterious process is the application of iPSCs. These extraordinary cellular entities provide a distinct advantage in our quest to unravel the secrets surrounding the onset of cancer, primarily because of their remarkable adaptability [45]. iPSCs possess the exceptional capacity to transform into the very cells from which various types of cancer originate. This unique attribute empowers researchers to explore the molecular and cellular mechanisms underpinning cancer initiation in ways that were previously considered unimaginable [15]. Nevertheless, it is of utmost importance for authors embarking on research in this field to address a pivotal query: What is the actual contribution of iPSCs to our comprehension of cancer initiation? This inquiry requires a thorough examination of the potential advantages and constraints inherent in investigations centered on iPSCs [45]. By engaging in this exploration, scientists can provide invaluable insights into the intricate landscape of cancer initiation. It is through this scrutiny that the genuine worth of iPSCs within the context of cancer research becomes evident. By elucidating the intricate interplay between genetic and environmental factors in the formation of cancerous cells, iPSCs offer a platform for examining the earliest phases of carcinogenesis, potentially paving the path for innovative therapeutic interventions and early detection methods [41]. Nonetheless, it is crucial to acknowledge the limitations associated with the use of iPSCs in unraveling the puzzle of cancer initiation. These limitations encompass challenges related to accurately replicating the microenvironment and epigenetic modifications occurring during the natural progression of cancer [45]. Furthermore, the inherent variability among different iPSC lines, in conjunction with the complexity of modeling various cancer types, emphasizes the need for cautious and meticulous experimental design [41]. While iPSCs present an unparalleled opportunity to shed light on cancer initiation, researchers must navigate a multifaceted terrain marked by subtleties and restrictions to effectively harness their full potential. By addressing these concerns, the scientific community can chart a more precise course towards harnessing the capabilities of iPSCs to illuminate the intricate aspects of cancer initiation [45].

Conclusion

The iPSCs have revolutionized the field of stem cell research and have shown tremendous potential in the development of new cancer therapies. In recent years, significant progress has been made in iPSC-based tumorigenesis research. Researchers have been able to generate iPSCs from cancer cells, providing a unique model for studying the molecular changes that occur during cancer development and progression. The iPSCs have also been used to develop personalized cancer therapies, allowing for targeted treatments based on a patient's specific genetic and epigenetic profiles. In addition, iPSCs have been used for drug screening, allowing for the identification of new compounds that may be effective in treating various types of cancer. Furthermore, iPSCs have been used to generate immune cells that can be used in immunotherapies, which have shown great promise in the treatment of certain types of cancer. iPSCs have also been used to develop cancer early detection methods, allowing for earlier diagnosis and treatment of cancer. The impact of iPSCs on the future of cancer research and treatment cannot be overstated. iPSCs offer a powerful tool for studying the molecular mechanisms of tumorigenesis and for developing new cancer therapies. The ability to generate iPSCs from cancer cells allows for the study of individual patient's tumors, leading to personalized treatments that may be more effective and have fewer side effects than current treatments. The iPSCs have also been used to develop immunotherapies, which have shown great promise in the treatment of certain types of cancer. Immunotherapies work by harnessing the power of the patient's own immune system to attack cancer cells. iPSCs can be used to generate immune cells that can be used in these therapies, providing a potential source of unlimited immune cells for cancer treatment. Furthermore, iPSCs offer a unique platform for drug screening and the development of new cancer treatments. By using iPSCs to generate different types of cells, researchers can test the efficacy and safety of potential new cancer drugs before testing them in animal models or human clinical trials. While iPSCs hold great promise in the field of cancer research and treatment, there are still many challenges that need to be overcome. One of the major challenges is the tumorigenic properties of iPSCs, which can lead to the formation of teratomas or other types of tumors. Additionally, the efficiency of iPSC generation needs to be improved, and the safety and efficacy of iPSC-based therapies need to be thoroughly evaluated. Continued investment in iPSC research is crucial to unlocking the full potential of these cells. Funding for iPSC research will allow for the development of new technologies and methods for generating iPSCs and for evaluating their safety and efficacy. In addition, continued investment in iPSC research will enable the development of new cancer therapies and the optimization of existing therapies. The iPSCs offer a powerful tool for studying tumorigenesis and for developing new cancer therapies. While significant progress has been made in iPSC-based tumorigenesis research, there are still many challenges that need to be overcome. Continued investment in iPSC research is crucial to unlocking the full potential of these cells and to realizing their promise in the field of cancer research and treatment. Some recommendations for future research include developing new methods for generating iPSCs that are safer and more efficient, improving the safety and efficacy of iPSC-based therapies, and developing new immunotherapies that utilize iPSC-generated immune cells. In addition, further research should focus on understanding the molecular changes that occur during cancer development and progression using iPSCs as a model. This will provide valuable insights into the mechanisms underlying tumorigenesis and help identify potential targets for therapeutic interventions. Moreover, it is important to explore the potential of iPSCs in combination with other treatment modalities. Combining iPSC-based therapies with existing cancer treatments, such as chemotherapy or radiation therapy, may enhance their effectiveness and improve patient outcomes. Additionally, investigating the synergistic effects of iPSC-derived immune cells with other immunotherapeutic approaches could lead to more robust and durable anti-cancer responses. Ethical and legal considerations surrounding iPSC research should also be addressed. As iPSCs can be derived from a patient's own cells, there are fewer ethical concerns compared to other types of stem cells. However, careful regulation and guidelines should be in place to ensure responsible and ethical use of iPSCs in research and clinical applications. In conclusion, iPSCs have demonstrated remarkable potential in the field of cancer research and therapy. The advancements made in iPSC-based tumorigenesis research have shed light on the complex processes involved in cancer development and have opened up new avenues for personalized medicine and innovative treatment strategies. However, there is still much work to be done to fully unlock the potential of iPSCs. Continued investment in iPSC research, both in terms of funding and collaboration between researchers and clinicians, is essential. This will enable further advancements in iPSC generation techniques, enhance our understanding of cancer biology, and facilitate the translation of iPSC-based therapies into clinical practice. With concerted efforts and ongoing research, iPSCs have the potential to revolutionize cancer treatment, improve patient outcomes, and ultimately contribute to the goal of eradicating cancer.

Availability of data and materials

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References

Rowe RG, Daley GQ. Induced pluripotent stem cells in disease modelling and drug discovery. Nat Rev Genet. 2019;20:377–88.
Article CAS PubMed PubMed Central Google Scholar
Li L, Papadopoulos V. Advances in stem cell research for the treatment of primary hypogonadism. Nat Rev Urol. 2021;18:487–507.
Article CAS PubMed Google Scholar
Lawrence M, Evans A, Moreau T, Bagnati M, Smart M, Hassan E, et al. Process analysis of pluripotent stem cell differentiation to megakaryocytes to make platelets applying European GMP. NPJ Regen Med. 2021;6:27.
Article PubMed PubMed Central Google Scholar
Chandrasekaran V, Carta G, da Costa PD, Gupta R, Murphy C, Feifel E, et al. Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability. Sci Rep. 2021;11:11575.
Article CAS PubMed PubMed Central Google Scholar
Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov. 2017;16:115–30.
Article CAS PubMed Google Scholar
Duff C, Baruteau J. Modelling urea cycle disorders using iPSCs. NPJ Regen Med. 2022;7:56.
Article CAS PubMed PubMed Central Google Scholar
de Rus JA, Denis HL, Cicchetti F, Alpaugh M. Current and future applications of induced pluripotent stem cell-based models to study pathological proteins in neurodegenerative disorders. Mol Psychiatry. 2021;26:2685–706.
Article Google Scholar
Hiratsuka K, Monkawa T, Akiyama T, Nakatake Y, Oda M, Goparaju SK, et al. Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. Sci Rep. 2019;9:913.
Article PubMed PubMed Central Google Scholar
Zhang W, Ross PJ, Ellis J, Salter MW. Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells. Transl Psychiatry. 2022;12:243.
Article CAS PubMed PubMed Central Google Scholar
Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, et al. Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases. Signal Transduct Target Ther. 2023;8:116.
Article PubMed PubMed Central Google Scholar
Araki R, Hoki Y, Suga T, Obara C, Sunayama M, Imadome K, et al. Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency. Nat Commun. 2020;11:197.
Article CAS PubMed PubMed Central Google Scholar
Taguchi J, Shibata H, Kabata M, Kato M, Fukuda K, Tanaka A, et al. DMRT1-mediated reprogramming drives development of cancer resembling human germ cell tumors with features of totipotency. Nat Commun. 2021;12:5041.
Article CAS PubMed PubMed Central Google Scholar
Supharattanasitthi W, Carlsson E, Sharif U, Paraoan L. CRISPR/Cas9-mediated one step bi-allelic change of genomic DNA in iPSCs and human RPE cells in vitro with dual antibiotic selection. Sci Rep. 2019;9:174.
Article PubMed PubMed Central Google Scholar
Maruoka S, Ojima T, Iwamoto H, Kitadani J, Tabata H, Tominaga S, et al. Tumor RNA transfected DCs derived from iPS cells elicit cytotoxicity against cancer cells induced from colorectal cancer patients in vitro. Sci Rep. 2022;12:3295.
Article CAS PubMed PubMed Central Google Scholar
Marin Navarro A, Susanto E, Falk A, Wilhelm M. Modeling cancer using patient-derived induced pluripotent stem cells to understand development of childhood malignancies. Cell death Discov. 2018;4:7.
Article PubMed PubMed Central Google Scholar
Ueda T, Shiina S, Iriguchi S, Terakura S, Kawai Y, Kabai R, et al. Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells. Nat Biomed Eng. 2023;7:24–37.
Article CAS PubMed Google Scholar
Ghosh S, Nehme R, Barrett LE. Greater genetic diversity is needed in human pluripotent stem cell models. Nat Commun. 2022;13(1):7301.
Article CAS PubMed PubMed Central Google Scholar
Wiegand C, Banerjee I. Recent advances in the applications of iPSC technology. Curr Opin Biotechnol. 2019;60:250–8.
Article CAS PubMed Google Scholar
Aboul-Soud MAM, Alzahrani AJ, Mahmoud A. Induced pluripotent stem cells (iPSCs)—roles in regenerative therapies, disease modelling and drug screening. Cells. 2021;10(9):2319.
Article CAS PubMed PubMed Central Google Scholar
Peñalosa-Ruiz G, Bright AR, Mulder KW, Veenstra GJC. The interplay of chromatin and transcription factors during cell fate transitions in development and reprogramming. Biochim Biophys Acta - Gene Regul Mech. 2019;1862: 194407.
Article PubMed Google Scholar
Lange L, Esteban MA, Schambach A. Back to pluripotency: fully chemically induced reboot of human somatic cells. Signal Transduct Target Ther. 2022;7:244.
Article PubMed PubMed Central Google Scholar
Fathi M, Riazi SS, Pourdamghan N. Triple-negative Breast Cancer Therapy Using RNA Nanoparticles Targeting Stem Cell Markers with Anti-miRNA: A Systematic Review and Meta-Analysis. Int J Sci Res Dent Med Sci. 2023;5(2):96–101.
CAS Google Scholar
Chakrabarty K, Shetty R, Argulwar S, Das D, Ghosh A. Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019. Cytotherapy. 2022;24:235–48.
Article CAS PubMed Google Scholar
Papapetrou EP. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med. 2016;22:1392–401.
Article CAS PubMed PubMed Central Google Scholar
Zhou Y, Li M, Zhou K, Brown J, Tsao T, Cen X, et al. Engineering induced pluripotent stem cells for cancer immunotherapy. Cancers (Basel). 2022;14(9):2266.
Article CAS PubMed Google Scholar
Sayed N, Liu C, Wu JC. Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine. J Am Coll Cardiol. 2016;67:2161–76.
Article PubMed PubMed Central Google Scholar
Sharkis SJ, Jones RJ, Civin C, Jang Y-Y. Pluripotent stem cell-based cancer therapy: promise and challenges. Sci Transl Med. 2012;4:127ps9.
Article PubMed PubMed Central Google Scholar
Griscelli F, Féraud O, Oudrhiri N, Gobbo E, Casal I, Chomel J-C, et al. Malignant germ cell-like tumors, expressing Ki-1 antigen (CD30), are revealed during in vivo differentiation of partially reprogrammed human-induced pluripotent stem cells. Am J Pathol. 2012;180:2084–96.
Article CAS PubMed Google Scholar
Câmara DAD, Mambelli LI, Porcacchia AS, Kerkis I. Advances and challenges on cancer cells reprogramming using induced pluripotent stem cells technologies. J Cancer. 2016;7:2296–303.
Article PubMed PubMed Central Google Scholar
Moquin-Beaudry G, Benabdallah B, Maggiorani D, Le O, Li Y, Colas C, et al. Autologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions. Cell Rep Methods. 2022;2: 100153.
Article CAS PubMed PubMed Central Google Scholar
Steeg R, Mueller SC, Mah N, Holst B, Cabrera-Socorro A, Stacey GN, et al. EBiSC best practice: How to ensure optimal generation, qualification, and distribution of iPSC lines. Stem Cell Rep. 2021;16:1853–67.
Article Google Scholar
Daley GQ, Hyun I, Apperley JF, Barker RA, Benvenisty N, Bredenoord AL, et al. Setting global standards for stem cell research and clinical translation: the 2016 ISSCR guidelines. Stem Cell Rep. 2016;6:787–97.
Article Google Scholar
Watanabe N, Santostefano KE, Yachnis AT, Terada N. A pathologist’s perspective on induced pluripotent stem cells. Lab Investig. 2017;97:1126–32.
Article PubMed Google Scholar
Biglari N, Mehdizadeh A, Mastanabad MV, Gharaeikhezri MH, Afrakoti LG, Pourbala H, et al. Application of mesenchymal stem cells (MSCs) in neurodegenerative disorders: history, findings, and prospective challenges. Pathol Res Pract. 2023:154541.
Wuputra K, Ku C-C, Wu D-C, Lin Y-C, Saito S, Yokoyama KK. Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells. J Exp Clin Cancer Res. 2020;39:1–24.
Article Google Scholar
Krog RT, de Miranda NFCC, Vahrmeijer AL, Kooreman NG. The potential of induced pluripotent stem cells to advance the treatment of pancreatic ductal adenocarcinoma. Cancers (Basel). 2021;13(22):5789.
Article CAS PubMed Google Scholar
Shamsian A, Sahebnasagh R, Norouzy A, Hussein SH, Ghahremani MH, Azizi Z. Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther. 2022;13:459.
Article PubMed PubMed Central Google Scholar
Fernandez TDS, De Souza Fernandez C, Mencalha AL. Human induced pluripotent stem cells from basic research to potential clinical applications in cancer. Biomed Res Int. 2013;2013:430290.
Article PubMed PubMed Central Google Scholar
Giacalone JC, Sharma TP, Burnight ER, Fingert JF, Mullins RF, Stone EM, et al. CRISPR-Cas9-based genome editing of human induced pluripotent stem cells. Curr Protoc Stem Cell Biol. 2018;44:5B.7.1-5B.7.22.
Article CAS PubMed Google Scholar
Bragança J, Lopes JA, Mendes-Silva L, Santos JMA. Induced pluripotent stem cells, a giant leap for mankind therapeutic applications. World J Stem Cells. 2019;11:421–30.
Article PubMed PubMed Central Google Scholar
Yoshihara M, Hayashizaki Y, Murakawa Y. Genomic Instability of iPSCs: challenges towards their clinical applications. Stem cell Rev reports. 2017;13:7–16.
Article CAS Google Scholar
Al Madhoun A, Sindhu S, Haddad D, Atari M, Ahmad R, Al-Mulla F. Dental pulp stem cells derived from adult human third molar tooth: a brief review. Front Cell Dev Biol. 2021;9:717624.
Casaroli-Marano RP, Nieto-Nicolau N, Martínez-Conesa EM, Edel M, Álvarez-Palomo BA. Potential role of Induced Pluripotent Stem Cells (IPSCs) for cell-based therapy of the ocular surface. J Clin Med. 2015;4:318–42.
Article CAS PubMed PubMed Central Google Scholar
Zhu K, Ma W, Li J, Zhang YS, Zhang W, Lai H, et al. Modeling aortic diseases using induced pluripotent stem cells. Stem Cells Transl Med. 2021;10:190–7.
Article PubMed Google Scholar
Virant-Klun I, Stimpfel M. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer. Sci Rep. 2016;6:34730.
Article CAS PubMed PubMed Central Google Scholar
Iberite F, Gruppioni E, Ricotti L. Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges. NPJ Regen Med. 2022;7:23.
Article PubMed PubMed Central Google Scholar
Kobayashi H, Nagao K, Nakajima K. Human Testis–Derived Pluripotent Cells and Induced Pluripotent Stem Cells. In: Bhartiya D, Lenka N, editors. Rijeka: IntechOpen; 2013. p. Ch. 6.
Gibler P, Gimble J, Hamel K, Rogers E, Henderson M, Wu X, et al. Human adipose-derived stromal/stem cell culture and analysis methods for adipose tissue modeling in vitro: a systematic review. Cells. 2021;10(6):1378.
Article CAS PubMed PubMed Central Google Scholar
Ghadami P, Mehrafar N, Rajabi H, Rabiee F, Eghbalifard N. Evaluation of the Effect of Mesenchymal Stem Cells on Breast Cancer Migration and Metastasis: A Systematic Review and Meta-analysis. Int J Sci Res Dent Med Sci. 2023;5(3):164–70.
Seidlitz T, Koo B-K, Stange DE. Gastric organoids—an in vitro model system for the study of gastric development and road to personalized medicine. Cell Death Differ. 2021;28:68–83.
Article PubMed Google Scholar
Audisio A, Buttigliero C, Delcuratolo MD, Parlagreco E, Audisio M, Ungaro A, et al. New perspectives in the medical treatment of non-muscle-invasive bladder cancer: immune checkpoint inhibitors and beyond. Cells. 2022;11(3):357.
Hepburn AC, Sims CHC, Buskin A, Heer R. Engineering prostate cancer from induced pluripotent stem cells—new opportunities to develop preclinical tools in prostate and prostate cancer studies. Int J Mol Sci. 2020;21(3):905.
Frappart P-O, Hofmann TG. Pancreatic Ductal Adenocarcinoma (PDAC) organoids: the shining light at the end of the tunnel for drug response prediction and personalized medicine. Cancers (Basel). 2020;12(10):2750.
Al PAGET, Goldsteen PA. REVIEW Human pluripotent stem cells for the modelling and treatment of respiratory diseases. 2021.
Google Scholar
Tian H, Lyu Y, Yang Y-G, Hu Z. Humanized rodent models for cancer research. Front Oncol. 2020;10:1696.
Article PubMed PubMed Central Google Scholar
Devika AS, Wruck W, Adjaye J, Sudheer S. The quest for pluripotency: a comparative analysis across mammalian species. Reproduction. 2019;158(3):R97–111.
Kumar D, Talluri TR, Selokar NL, Hyder I, Kues WA. Perspectives of pluripotent stem cells in livestock. World J Stem Cells. 2021;13:1.
Article PubMed PubMed Central Google Scholar
Fu J, Warmflash A, Lutolf MP. Stem-cell-based embryo models for fundamental research and translation. Nat Mater. 2021;20:132–44.
Article PubMed Google Scholar
Gania Z, Noorintan ST, Septiari NP, Fitriany DS, Torizal FG. Strategies for generating human pluripotent stem cell-derived-organoid culture for disease modeling, drug screening, and regenerative therapy. Futur Pharmacol. 2022;2:360–76.
Article Google Scholar
Scarfone RA, Pena SM, Russell KA, Betts DH, Koch TG. The use of induced pluripotent stem cells in domestic animals: a narrative review. BMC Vet Res. 2020;16:477.
Article PubMed PubMed Central Google Scholar
Cappella M, Elouej S, Biferi MG. The potential of induced pluripotent stem cells to test gene therapy approaches for neuromuscular and motor neuron disorders. Front Cell Dev Biol. 2021;9: 662837.
Article PubMed PubMed Central Google Scholar
Pandelakis M, Delgado E, Ebrahimkhani MR. CRISPR-based synthetic transcription factors in vivo: the future of therapeutic cellular programming. Cell Syst. 2020;10:1–14.
Article CAS PubMed PubMed Central Google Scholar
Shaw SWS, Cheng P-J, Chang Y-L, Chao A-S, Wang T-H, Chang S-D, et al. Human amniotic fluid stem cells have better potential in early second trimester of pregnancy and can be reprogramed to iPS. Taiwan J Obstet Gynecol. 2017;56:770–4.
Article PubMed Google Scholar
Pieri NCG, de Souza AF, Botigelli RC, Pessôa LV, Recchia K, Machado LS, et al. Porcine primordial germ cell-like cells generated from induced pluripotent stem cells under different culture conditions. Stem Cell Rev Reports. 2022;18:1639–56.
Article CAS Google Scholar
Amini Mahabadi J, Sabzalipoor H, Kehtari M, Enderami SE, Soleimani M, Nikzad H. Derivation of male germ cells from induced pluripotent stem cells by inducers: a review. Cytotherapy. 2018;20:279–90.
Article CAS PubMed Google Scholar
Trokovic R, Weltner J, Otonkoski T. Generation of iPSC line HEL24.3 from human neonatal foreskin fibroblasts. Stem Cell Res. 2015;15:266–8.
Article CAS PubMed Google Scholar
Xu C, Tabebordbar M, Iovino S, Ciarlo C, Liu J, Castiglioni A, et al. A zebrafish embryo culture system defines factors that promote vertebrate myogenesis across species. Cell. 2013;155:909–21.
Article CAS PubMed PubMed Central Google Scholar
Garcia-Leon JA, Caceres-Palomo L, Sanchez-Mejias E, Mejias-Ortega M, Nuñez-Diaz C, Fernandez-Valenzuela JJ, et al. Human pluripotent stem cell-derived neural cells as a relevant platform for drug screening in alzheimer’s disease. Int J Mol Sci. 2020;21(18):6867.
Article CAS PubMed PubMed Central Google Scholar
Liang Y, Tan F, Sun X, Cui Z, Gu J, Mao S, et al. Aberrant retinal pigment epithelial cells derived from induced pluripotent stem cells of a retinitis pigmentosa patient with the PRPF6 mutation. Int J Mol Sci. 2022;23(16):9049.
Article CAS PubMed PubMed Central Google Scholar
Luciani A, Freedman BS. Induced pluripotent stem cells provide mega insights into kidney disease. Kidney Int. 2020;98:54–7.
Article CAS PubMed PubMed Central Google Scholar
Tanaka J, Senpuku H, Ogawa M, Yasuhara R, Ohnuma S, Takamatsu K, et al. Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication. Nat Cell Biol. 2022;24:1595–605.
Article CAS PubMed Google Scholar
Ribeiro PD, Lojudice FH, Fernandes-Charpiot IMM, Baptista MASF, de Almeida Araújo S, Mendes GEF, et al. Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease. Stem Cell Res Ther. 2020;11:530.
Article CAS PubMed PubMed Central Google Scholar
Hu J, Zhao Q, Feng Y, Li N, Gu Y, Sun R, et al. Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells. Sci Rep. 2018;8:10955.
Article PubMed PubMed Central Google Scholar
Groß B, Pittermann E, Reinhardt D, Cantz T, Klusmann J-H. Prospects and challenges of reprogrammed cells in hematology and oncology. Pediatr Hematol Oncol. 2012;29:507–28.
Article PubMed Google Scholar
Dehghan S, Mirshahi R, Shoae-Hassani A, Naseripour M. Human-induced pluripotent stem cells-derived retinal pigmented epithelium, a new horizon for cells-based therapies for age-related macular degeneration. Stem Cell Res Ther. 2022;13:217.
Article PubMed PubMed Central Google Scholar
Mitsui K, Ide K, Takahashi T, Kosai K. Viral vector-based innovative approaches to directly abolishing tumorigenic cells: novel technologies for safer clinical application of pluripotent stem cell-based regenerative medicine. Mol Ther Methods Clin Dev. 2017;5:51–8. https://doi.org/10.1016/j.omtm.2017.03.002.
Sharp B, Rallabandi R, Devaux P. Advances in RNA viral vector technology to reprogram somatic cells: the paramyxovirus wave. Mol Diagn Ther. 2022;26:353–67.
Article CAS PubMed Google Scholar
de l’Hortet AC, Takeishi K, Guzman-Lepe J, Morita K, Achreja A, Popovic B, et al. Generation of human fatty livers using custom-engineered induced pluripotent stem cells with modifiable SIRT1 metabolism. Cell Metab. 2019;30:385–401.
Article Google Scholar
Lawlor N, Márquez EJ, Orchard P, Narisu N, Shamim MS, Thibodeau A, et al. Multiomic profiling identifies cis-regulatory networks underlying human pancreatic β cell identity and function. Cell Rep. 2019;26:788-801.e6.
Article CAS PubMed PubMed Central Google Scholar
Vu M, Li R, Baskfield A, Lu B, Farkhondeh A, Gorshkov K, et al. Neural stem cells for disease modeling and evaluation of therapeutics for Tay-Sachs disease. Orphanet J Rare Dis. 2018;13:152.
Article PubMed PubMed Central Google Scholar
Liu X, Li C, Zheng K, Zhao X, Xu X, Yang A, et al. Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells. Cell Div. 2020;15:12.
Article CAS PubMed PubMed Central Google Scholar
Olgasi C, Cucci A, Follenzi A. iPSC-derived liver organoids: a journey from drug screening, to disease modeling, arriving to regenerative medicine. Int J Mol Sci. 2020;21(17):6215.
Article CAS PubMed PubMed Central Google Scholar
Ezashi T, Telugu BPVL, Alexenko AP, Sachdev S, Sinha S, Roberts RM. Derivation of induced pluripotent stem cells from pig somatic cells. Proc Natl Acad Sci U S A. 2009;106:10993–8.
Article CAS PubMed PubMed Central Google Scholar
Isoda M, Sanosaka T, Tomooka R, Mabuchi Y, Shinozaki M, Andoh-Noda T, et al. Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation. Commun Biol. 2023;6:1–15.
Article Google Scholar
Romayor I, Herrera L, Burón M, Martin-Inaraja M, Prieto L, Etxaniz J, et al. A comparative study of cell culture conditions during conversion from primed to naive human pluripotent stem cells. Biomedicines. 2022;10(6):1358.
Article CAS PubMed PubMed Central Google Scholar
Abad M, Mosteiro L, Pantoja C, Cañamero M, Rayon T, Ors I, et al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature. 2013;502:340–5.
Article CAS PubMed Google Scholar
Bogliotti YS, Wu J, Vilarino M, Okamura D, Soto DA, Zhong C, et al. Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts. Proc Natl Acad Sci U S A. 2018;115:2090–5.
Article CAS PubMed PubMed Central Google Scholar
Okita K, Yamanaka S. Intracellular signaling pathways regulating pluripotency of embryonic stem cells. Curr Stem Cell Res Ther. 2006;1:103–11.
Article CAS PubMed Google Scholar
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.
Article CAS PubMed Google Scholar
Ohnuki M, Takahashi K. Present and future challenges of induced pluripotent stem cells. Philos Trans R Soc London Ser B, Biol Sci. 2015;370:20140367.
Article Google Scholar
Eguchi A, Gonzalez AFGS, Torres-Bigio SI, Koleckar K, Birnbaum F, Zhang JZ, et al. TRF2 rescues telomere attrition and prolongs cell survival in Duchenne muscular dystrophy cardiomyocytes derived from human iPSCs. Proc Natl Acad Sci U S A. 2023;120:e2209967120.
Article CAS PubMed PubMed Central Google Scholar
Chakritbudsabong W, Chaiwattanarungruengpaisan S, Sariya L, Pamonsupornvichit S, Ferreira JN, Sukho P, et al. Exogenous LIN28 is required for the maintenance of self-renewal and pluripotency in presumptive porcine-induced pluripotent stem cells. Front Cell Dev Biol. 2021;9: 709286.
Article PubMed PubMed Central Google Scholar
Staal FJT, Baum C, Cowan C, Dzierzak E, Hacein-Bey-Abina S, Karlsson S, et al. Stem cell self-renewal: lessons from bone marrow, gut and iPS toward clinical applications. Leukemia. 2011;25:1095–102.
Article CAS PubMed Google Scholar
Lee J-H, Lee JB, Shapovalova Z, Fiebig-Comyn A, Mitchell RR, Laronde S, et al. Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states. Nat Commun. 2014;5:5605.
Article CAS PubMed Google Scholar
Luo Y, Zhang M, Chen Y, Chen Y, Zhu D. Application of human induced pluripotent stem cell-derived cellular and organoid models for COVID-19 research. Front cell Dev Biol. 2021;9: 720099.
Article PubMed PubMed Central Google Scholar
Yao C, Yao R, Luo H, Shuai L. Germline specification from pluripotent stem cells. Stem Cell Res Ther. 2022;13:74.
Article PubMed PubMed Central Google Scholar
Rore H, Owen N, Piña-Aguilar RE, Docherty K, Sekido R. Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells. Commun Biol. 2021;4:802.
Article CAS PubMed PubMed Central Google Scholar
Markowska J, Kojs Z, Twardawa D. Cancer stem cells in targeted therapy. Curr Gynecol Oncol. 2018;16:96–100.
Article Google Scholar
Wilkinson AC, Igarashi KJ, Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat Rev Genet. 2020;21:541–54.
Article CAS PubMed PubMed Central Google Scholar
Tian Z, Guo F, Biswas S, Deng W. Rationale and methodology of reprogramming for generation of induced pluripotent stem cells and induced neural progenitor cells. Int J Mol Sci. 2016;17:594.
Article PubMed PubMed Central Google Scholar
Polanco A, Kuang B, Yoon S. Bioprocess technologies that preserve the quality of iPSCs. Trends Biotechnol. 2020;38:1128–40.
Article CAS PubMed Google Scholar
Liu H, Kim Y, Sharkis S, Marchionni L, Jang Y-Y. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci Transl Med. 2011;3:82ra39.
Article PubMed PubMed Central Google Scholar
Xu J, Yu L, Guo J, Xiang J, Zheng Z, Gao D, et al. Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system. Stem Cell Res Ther. 2019;10:193.
Article PubMed PubMed Central Google Scholar
Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, et al. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nat Commun. 2021;12:430.
Article CAS PubMed PubMed Central Google Scholar
Turhan AG, Hwang JW, Chaker D, Tasteyre A, Latsis T, Griscelli F, et al. iPSC-derived organoids as therapeutic models in regenerative medicine and oncology. Front Med. 2021;8: 728543.
Article Google Scholar
Che YH, Lee H, Kim YJ. New insights into the epitranscriptomic control of pluripotent stem cell fate. Exp Mol Med. 2022;54:1643–51.
Article CAS PubMed PubMed Central Google Scholar
Fang Y-H, Wang SPH, Gao Z-H, Wu S-N, Chang H-Y, Yang P-J, et al. Efficient cardiac differentiation of human amniotic fluid-derived stem cells into induced pluripotent stem cells and their potential immune privilege. Int J Mol Sci. 2020;21(7):2359.
Article CAS PubMed PubMed Central Google Scholar
Lai HIAM, Chou S-J, Chien Y, Tsai P-H, Chien C-S, Hsu C-C, et al. Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids. Int J Mol Sci. 2021;22:1–18.
Google Scholar
Kooreman NG, Kim Y, de Almeida PE, Termglinchan V, Diecke S, Shao N-Y, et al. Autologous iPSC-based vaccines elicit anti-tumor responses in vivo. Cell Stem Cell. 2018;22:501-513.e7.
Article CAS PubMed PubMed Central Google Scholar
Sackett SD, Brown ME, Tremmel DM, Ellis T, Burlingham WJ, Odorico JS. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation. Transplant Rev. 2016;30:61–70.
Article CAS Google Scholar
Murata K, Ikegawa M, Minatoya K, Masumoto H. Strategies for immune regulation in iPS cell-based cardiac regenerative medicine. Inflamm Regen. 2020;40:36.
Article CAS PubMed PubMed Central Google Scholar
Menon DV, Patel D, Joshi CG, Kumar A. The road less travelled: The efficacy of canine pluripotent stem cells. Exp Cell Res. 2019;377:94–102.
Article CAS PubMed Google Scholar
Wang B, Iriguchi S, Waseda M, Ueda N, Ueda T, Xu H, et al. Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells. Nat Biomed Eng. 2021;5:429–40.
Article CAS PubMed Google Scholar
Yucer N, Ahdoot R, Workman MJ, Laperle AH, Recouvreux MS, Kurowski K, et al. Human iPSC-derived fallopian tube organoids with BRCA1 mutation recapitulate early-stage carcinogenesis. Cell Rep. 2021;37: 110146.
Article CAS PubMed PubMed Central Google Scholar
Touhidul Islam M, Nahar Sultana GN, Khan R, Islam A, Mahmud H, Zahir Raihan S. Study on mitochondrial ATPase6 gene polymorphisms as a genetic risk factor for breast cancer in Bangladeshi women. Int J Sci Res Dent Med Sci. 2021;3(1):18–22.
Barchiesi G, Roberto M, Verrico M, Vici P, Tomao S, Tomao F. Emerging role of PARP inhibitors in metastatic triple negative breast cancer. Current scenario and future perspectives. Front Oncol. 2021;11:769280.
Article CAS PubMed PubMed Central Google Scholar
Osude C, Lin L, Patel M, Eckburg A, Berei J, Kuckovic A, et al. Mediating EGFR-TKI resistance by VEGF/VEGFR autocrine pathway in non-small cell lung cancer. Cells. 2022;11(10):1694.
Article CAS PubMed PubMed Central Google Scholar
Telliam G, Desterke C, Imeri J, M’kacher R, Oudrhiri N, Balducci E, et al. Modeling global genomic instability in Chronic Myeloid Leukemia (CML) using patient-derived Induced Pluripotent Stem Cells (iPSCs). Cancers. 2023;15:2594.
Article CAS PubMed PubMed Central Google Scholar
Telliam G, Féraud O, Baykal-Köse S, Griscelli F, Imeri J, Latsis T, et al. Evidence of Increased Hemangioblastic and Early Hematopoietic Potential in Chronic Myeloid Leukemia (CML)-derived Induced Pluripotent Stem Cells (iPSC). StemJournal. 2022;4:13–26.
Article Google Scholar
Malaquin N, Vancayseele A, Gilbert S, Antenor-Habazac L, Olivier M-A, Ait Ali Brahem Z, et al. DNA Damage- but not enzalutamide-induced senescence in prostate cancer promotes senolytic Bcl-xL inhibitor sensitivity. Cells. 2020;9(7):1593.
Article CAS PubMed PubMed Central Google Scholar
Zimmermannova O, Caiado I, Ferreira AG, Pereira C-F. Cell fate reprogramming in the era of cancer immunotherapy. Front Immunol. 2021;12: 714822.
Article PubMed PubMed Central Google Scholar
Hassan G, Ohara T, Afify SM, Kumon K, Zahra MH, Fu X, et al. Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways. J Exp Clin Cancer Res. 2022;41:29.
Article CAS PubMed PubMed Central Google Scholar
Yang J, Huang S, Cheng S, Jin Y, Zhang N, Wang Y. Application of ovarian cancer organoids in precision medicine: key challenges and current opportunities. Front cell Dev Biol. 2021;9: 701429.
Article PubMed PubMed Central Google Scholar
Brodeur MN, Simeone K, Leclerc-Deslauniers K, Fleury H, Carmona E, Provencher DM, et al. Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models. Sci Rep. 2021;11:18183.
Article CAS PubMed PubMed Central Google Scholar
Plummer S, Wallace S, Ball G, Lloyd R, Schiapparelli P, Quiñones-Hinojosa A, et al. A human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. Sci Rep. 2019;9:1407.
Article PubMed PubMed Central Google Scholar
Raue KD, Duffy JT, Babak MV, Balyasnikova IV. Modeling glioblastoma complexity with organoids for personalized treatments. Trends Mol Med. 2023;29(4):282–96.
Article CAS Google Scholar
Braun LM, Lagies S, Guenzle J, Fichtner-Feigl S, Wittel UA, Kammerer B. Metabolic adaptation during nab-Paclitaxel resistance in pancreatic cancer cell lines. Cells. 2020;9(5):125.
Article Google Scholar
Goldenson BH, Hor P, Kaufman DS. iPSC-derived natural killer cell therapies-expansion and targeting. Front Immunol. 2022;13:841107.
King JL, Benhabbour SR. Glioblastoma multiforme—a look at the past and a glance at the future. Pharmaceutics. 2021;13(7):1053.
Article CAS PubMed PubMed Central Google Scholar
Zhu J, Ji L, Chen Y, Li H, Huang M, Dai Z, et al. Organoids and organs-on-chips: insights into predicting the efficacy of systemic treatment in colorectal cancer. Cell Death Discov. 2023;9:72.
Article PubMed PubMed Central Google Scholar
Maddineni S, Silberstein JL, Sunwoo JB. Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells. J Immunother Cancer. 2022;10(5).
Bernareggi D, Yun J, Goldenson B, Kaufman DS. Knock-in of the BCL2 G101V mutation in human iPSC-derived NK cells generates venetoclax resistance and improves activity against venetoclax resistant AML. Blood. 2022;140:7407–8.
Article Google Scholar
Agostini A, Orlacchio A, Carbone C, Guerriero I. Understanding tricky cellular and molecular interactions in pancreatic tumor microenvironment: new food for thought. Front Immunol. 2022;13:876291.
Article CAS PubMed PubMed Central Google Scholar
Boix-Montesinos P, Soriano-Teruel PM, Armiñán A, Orzáez M, Vicent MJ. The past, present, and future of breast cancer models for nanomedicine development. Adv Drug Deliv Rev. 2021;173:306–30.
Article CAS PubMed PubMed Central Google Scholar
Lai C-J, Lin C-Y, Liao W-Y, Hour T-C, Wang H-D, Chuu C-P. CD44 promotes migration and invasion of docetaxel-resistant prostate cancer cells likely via induction of Hippo-Yap signaling. Cells. 2019;8(4):295.
Article CAS PubMed PubMed Central Google Scholar
Chen K, Li Y, Wang B, Yan X, Tao Y, Song W, et al. Patient-derived models facilitate precision medicine in liver cancer by remodeling cell-matrix interaction. Front Immunol. 2023;14:1101324.
Article CAS PubMed PubMed Central Google Scholar
Li L, Wang Y, Jiao L, Lin C, Lu C, Zhang K, et al. Autophagy determines osimertinib resistance through regulation of stem cell-like properties in EGFR-mutant lung cancer. bioRxiv. 2018;330092.
Verduin M, Hoeben A, De Ruysscher D, Vooijs M. Patient-derived cancer organoids as predictors of treatment response. Front Oncol. 2021;820.
Akay M, Funingana I-G, Patel G, Mustapha R, Gjafa E, Ng T, et al. An in-depth review of niraparib in ovarian cancer: mechanism of action, clinical efficacy and future directions. Oncol Ther. 2021;9:347–64.
Article PubMed PubMed Central Google Scholar
Fallahi-Sichani M, Becker V, Izar B, Baker GJ, Lin J, Boswell SA, et al. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state. Mol Syst Biol. 2017;13:905.
Article PubMed PubMed Central Google Scholar
Castro-Pérez E, Rodríguez CI, Mikheil D, Siddique S, McCarthy A, Newton MA, et al. Melanoma progression inhibits pluripotency and differentiation of melanoma-derived iPSCs produces cells with neural-like mixed dysplastic phenotype. Stem Cell Reports. 2019;13:177–92.
Article PubMed PubMed Central Google Scholar
Sobhani N, D’Angelo A, Pittacolo M, Roviello G, Miccoli A, Corona SP, et al. Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer. Cells. 2019;8(4):321.
Article CAS PubMed PubMed Central Google Scholar
Conteduca V, Mosca A, Brighi N, de Giorgi U, Rescigno P. New prognostic biomarkers in metastatic castration-resistant prostate cancer. Cells. 2021;10:193.
Article CAS PubMed PubMed Central Google Scholar
Ito K, Nagata K, Ohta S, Matsuda Y, Ukai T, Yasuda I, et al. The oncogene-dependent resistance to reprogramming unveils cancer therapeutic targets. Cell Rep. 2022;39: 110721.
Article CAS PubMed Google Scholar
Hofman P. Detecting resistance to therapeutic ALK inhibitors in tumor tissue and liquid biopsy markers: an update to a clinical routine practice. Cells. 2021;10(1):168.
Article CAS PubMed PubMed Central Google Scholar
Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 2019;16:361–75.
Article PubMed PubMed Central Google Scholar
Rodriguez-Aznar E, Wiesmüller L, Sainz B, Hermann PC. EMT and stemness—key players in pancreatic cancer stem cells. Cancers (Basel). 2019;11(8):113.
Article Google Scholar
Moccia C, Haase K. Engineering breast cancer on-chip—moving toward subtype specific models. Front Bioeng Biotechnol. 2021;9: 694218.
Article PubMed PubMed Central Google Scholar
Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M. Paclitaxel-based chemotherapy targeting cancer stem cells from mono- to combination therapy. Biomedicines. 2021;9(5):500.
Article CAS PubMed PubMed Central Google Scholar
Cha TL, Wu TTL, Vogelzang NJ, Huang CY, Huang SP, Lin CC, et al. Optimal usage of radium-223 in metastatic castration-resistant prostate cancer. J Formos Med Assoc. 2017;116:825–36.
Article CAS PubMed Google Scholar
Gristina V, La Mantia M, Iacono F, Galvano A, Russo A, Bazan V. The emerging therapeutic landscape of ALK inhibitors in non-small cell lung cancer. Pharmaceuticals. 2020;13(12):474.
Article CAS PubMed PubMed Central Google Scholar
Roviello G, D’Angelo A, Petrioli R, Roviello F, Cianchi F, Nobili S, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. Transl Oncol. 2020;13: 100795.
Article PubMed PubMed Central Google Scholar
Garcia-Carbonero N, Martinez-Useros J, Li W, Orta A, Perez N, Carames C, et al. KRAS and BRAF mutations as prognostic and predictive biomarkers for standard chemotherapy response in metastatic colorectal cancer: a single institutional study. Cells. 2020;9(1):219.
Article CAS PubMed PubMed Central Google Scholar
Chmiel P, Gęca K, Rawicz-Pruszyński K, Polkowski WP, Skórzewska M. FGFR inhibitors in cholangiocarcinoma–a novel yet primary approach: where do we stand now and where to head next in targeting this axis? Cells. 2022;11(23):3929.
Article CAS PubMed PubMed Central Google Scholar
Mercogliano MF, Bruni S, Mauro FL, Schillaci R. Emerging targeted therapies for HER2-positive breast cancer. Cancers (Basel). 2023;15(7):1987.
Article CAS PubMed Google Scholar
Seo E, Kang M. Current status and clinical application of patient-derived tumor organoid model in kidney and prostate cancers. BMB Rep. 2023;56:24–31.
Article CAS PubMed Google Scholar
Dupont CA, Riegel K, Pompaiah M, Juhl H, Rajalingam K. Druggable genome and precision medicine in cancer: current challenges. FEBS J. 2021;288:6142–58.
Article CAS PubMed Google Scholar
Azwar S, Seow HF, Abdullah M, Faisal Jabar M, Mohtarrudin N. Recent updates on mechanisms of resistance to 5-Fluorouracil and reversal strategies in colon cancer treatment. Biology (Basel). 2021;10(9):854.
CAS PubMed Google Scholar
Ciucci A, Buttarelli M, Fagotti A, Scambia G, Gallo D. Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application. Cell Mol Life Sci. 2022;79:364.
Article CAS PubMed PubMed Central Google Scholar
Liu X, Lu Y, Qin S. Atezolizumab and bevacizumab for hepatocellular carcinoma: Mechanism, pharmacokinetics and future treatment strategies. Futur Oncol. 2021;17:2243–56.
Article CAS Google Scholar
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.
Article CAS PubMed Google Scholar
Romero-Calvo I, Weber CR, Ray M, Brown M, Kirby K, Nandi RK, et al. Human organoids share structural and genetic features with primary pancreatic adenocarcinoma tumorsPDAC organoids mimic patient disease. Mol Cancer Res. 2019;17:70–83.
Article CAS PubMed Google Scholar
Pan L, Han J, Lin M. Targeting breast cancer stem cells in refractory breast cancer. Front Oncol. 2023;13:17.
Article Google Scholar
Corti C, Venetis K, Sajjadi E, Zattoni L, Curigliano G, Fusco N. CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress. Expert Opin Investig Drugs. 2022;31:593–605.
Article CAS PubMed Google Scholar
Lemmens G, Brouwers J, Snoeys J, Augustijns P, Vanuytsel T. Insight into the colonic disposition of celecoxib in humans. Eur J Pharm Sci. 2020;145: 105242.
Article CAS PubMed Google Scholar
Biegała Ł, Gajek A, Marczak A, Rogalska A. Olaparib-resistant BRCA2MUT ovarian cancer cells with restored BRCA2 abrogate olaparib-induced DNA damage and G2/M arrest controlled by the ATR/CHK1 pathway for survival. Cells. 2023;12(7):1038.
Article PubMed PubMed Central Google Scholar
Intabli H, Gee JM, Oesterreich S, Yeoman MS, Allen MC, Qattan A, et al. Glucocorticoid induced loss of oestrogen receptor alpha gene methylation and restoration of sensitivity to fulvestrant in triple negative breast cancer. Gene. 2023;851: 147022.
Article CAS PubMed Google Scholar
Rice MA, Kumar V, Tailor D, Garcia-Marques FJ, Hsu E-C, Liu S, et al. SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer. Cell Reports Med. 2022;3: 100502.
Article CAS Google Scholar
D’Angelo A, Sobhani N, Chapman R, Bagby S, Bortoletti C, Traversini M, et al. Focus on ROS1-positive non-small cell lung cancer (NSCLC): crizotinib, resistance mechanisms and the newer generation of targeted therapies. Cancers (Basel). 2020;12:3293.
Article PubMed Google Scholar
Kehagias P, Kindt N, Krayem M, Najem A, Agostini G, Acedo Reina E, et al. Regorafenib induces senescence and epithelial-mesenchymal transition in colorectal cancer to promote drug resistance. Cells. 2022;11(22):3663.
Article CAS PubMed PubMed Central Google Scholar
Liu Y-C, Tsai J-J, Weng Y-S, Hsu F-T. Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer. Biomed Pharmacother. 2020;128: 110319.
Article CAS PubMed Google Scholar
Baiao A, Dias S, Soares AF, Pereira CL, Oliveira C, Sarmento B. Advances in the use of 3D colorectal cancer models for novel drug discovery. Expert Opin Drug Discov. 2022;17:569–80.
Article CAS PubMed Google Scholar
Wei Y, Erfani S, Schweer D, de Gouvea R, Qadir J, Shi J, et al. Targeting receptor tyrosine kinases in ovarian cancer: genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies. Mol Ther. 2023;28:293–306.
Google Scholar
Rountree CB, Mishra L, Willenbring H. Stem cells in liver diseases and cancer: recent advances on the path to new therapies. Hepatology. 2012;55:298–306.
Article PubMed Google Scholar
Alzhrani R, Alsaab HO, Vanamala K, Bhise K, Tatiparti K, Barari A, et al. Overcoming the tumor microenvironmental barriers of pancreatic ductal adenocarcinomas for achieving better treatment outcomes. Adv Ther. 2021;4:2000262.
Article Google Scholar
Pai Bellare G, Sankar PB. Resveratrol sensitizes breast cancer to PARP inhibitor, talazoparib through dual inhibition of AKT and autophagy flux. Biochem Pharmacol. 2022;199: 115024.
Article CAS PubMed Google Scholar
Zhang D, Singh B, Moerland J, Mitchell O, Lockwood L, Carapellucci S, et al. Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in Brca1-deficient mice. Sci Rep. 2021;11:1234.
Article CAS PubMed PubMed Central Google Scholar
Campbell CM, Zhang KW, Collier A, Linch M, Calaway AC, Ponsky L, et al. Cardiovascular complications of prostate cancer therapy. Curr Treat Options Cardiovasc Med. 2020;22:69.
Article Google Scholar
Zhu K, Lv Z, Xiong J, Zheng H, Zhang S, Jin H, et al. MET inhibitor, capmatinib overcomes osimertinib resistance via suppression of MET/Akt/snail signaling in non-small cell lung cancer and decreased generation of cancer-associated fibroblasts. Aging (Albany NY). 2021;13:6890–903.
Article CAS PubMed Google Scholar
Grothey A, Fakih M, Tabernero J. Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines. Ann Oncol. 2021;32:959–67.
Article CAS PubMed Google Scholar
Han C, Bellone S, Zammataro L, Schwartz PE, Santin AD. Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment. Gynecol Oncol Reports. 2018;25:41–4.
Article Google Scholar
Choi SR, Yang Y, Huang KY, Kong HJ, Flick MJ, Han B. Engineering of biomaterials for tumor modeling. Mater Today Adv. 2020;8: 100117.
Article PubMed PubMed Central Google Scholar
Guo H, Zhang J, Qin C, Yan H, Liu T, Hu H, et al. Biomarker-targeted therapies in non-small cell lung cancer: current status and perspectives. Cells. 2022;11:3200.
Article CAS PubMed PubMed Central Google Scholar
Maher J, Davies DM. CAR-based immunotherapy of solid tumours—a survey of the emerging targets. Cancers (Basel). 2023;15:1171.
Article CAS PubMed Google Scholar
Bhan A, Ansari K, Chen MY, Jandial R. Human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively target HER2+ breast cancer metastasis to the brain. Sci Rep. 2021;11:16866.
Article CAS PubMed PubMed Central Google Scholar
Nicola C, Dubois M, Campart C, Al Sagheer T, Desrues L, Schapman D, et al. The prostate cancer therapy enzalutamide compared with abiraterone acetate/prednisone impacts motivation for exploration, spatial learning and alters dopaminergic transmission in aged castrated mice. Cancers (Basel). 2021;13(14):3518.
Article CAS PubMed Google Scholar
Farnsworth DA, Chen YT, de Rappard Yuswack G, Lockwood WW. Emerging molecular dependencies of mutant EGFR-driven non-small cell lung cancer. Cells. 2021;10(12):3553.
Article CAS PubMed PubMed Central Google Scholar
Ellinghaus P, Neureiter D, Nogai H, Stintzing S, Ocker M. Patient selection approaches in FGFR inhibitor trials-many paths to the same end? Cells. 2022;11(19):3180.
Article CAS PubMed PubMed Central Google Scholar
Kung H, Yu J. Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study. MedComm. 2023;4: e216.
Article CAS PubMed PubMed Central Google Scholar
Jost T, Heinzerling L, Fietkau R, Hecht M, Distel LV. Palbociclib induces senescence in melanoma and breast cancer cells and leads to additive growth arrest in combination with irradiation. Front Oncol. 2021;11: 740002.
Article CAS PubMed PubMed Central Google Scholar
Alkhudair NA. Apalutamide: emerging therapy for non-metastatic castration-resistant prostate cancer. Saudi Pharm J. 2019;27:368–72.
Article PubMed Google Scholar
Wu J, Lin Z. Non-small cell lung cancer targeted therapy: drugs and mechanisms of drug resistance. Int J Mol Sci. 2022;23(23):15056.
Article CAS PubMed PubMed Central Google Scholar
Baci D, Bosi A, Gallazzi M, Rizzi M, Noonan DM, Poggi A, et al. The ovarian cancer Tumor Immune Microenvironment (TIME) as target for therapy: a focus on innate immunity cells as therapeutic effectors. Int J Mol Sci. 2020;21(9):3125.
Article CAS PubMed PubMed Central Google Scholar
Liu Z, Liu X, Liang J, Liu Y, Hou X, Zhang M, et al. Immunotherapy for hepatocellular carcinoma: current status and future prospects. Front Immunol. 2021;12: 765101.
Article CAS PubMed PubMed Central Google Scholar
Lin X, Stenvang J, Rasmussen MH, Zhu S, Jensen NF, Tarpgaard LS, et al. The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer. BMC Genomics. 2015;16:404.
Article PubMed PubMed Central Google Scholar
Nie Y-Z, Zheng Y-W, Miyakawa K, Murata S, Zhang R-R, Sekine K, et al. Recapitulation of hepatitis B virus–host interactions in liver organoids from human induced pluripotent stem cells. EBioMedicine. 2018;35:114–23.
Article PubMed PubMed Central Google Scholar
Sally Á, McGowan R, Finn K, Moran BM. Current and future therapies for pancreatic ductal adenocarcinoma. Cancers (Basel). 2022;14(10):2417.
Article CAS PubMed Google Scholar
Grimm FA, Iwata Y, Sirenko O, Bittner M, Rusyn I. High-content assay multiplexing for toxicity screening in induced pluripotent stem cell-derived cardiomyocytes and hepatocytes. Assay Drug Dev Technol. 2015;13:529–46.
Article CAS PubMed PubMed Central Google Scholar
Lin M, Xiong W, Wang S, Li Y, Hou C, Li C, et al. The research progress of trastuzumab-induced cardiotoxicity in HER-2-positive breast cancer treatment. Front Cardiovasc Med. 2022;8:2075.
Article Google Scholar
Chung C-T, Yeh K-C, Lee C-H, Chen Y-Y, Ho P-J, Chang K-Y, et al. Molecular profiling of afatinib-resistant non-small cell lung cancer cells in vivo derived from mice. Pharmacol Res. 2020;161: 105183.
Article CAS PubMed Google Scholar
Reyes-González JM, Quiñones-Díaz BI, Santana Y, Báez-Vega PM, Soto D, Valiyeva F, et al. Downstream effectors of ILK in cisplatin-resistant ovarian cancer. Cancers (Basel). 2020;12(4):880.
Article PubMed Google Scholar
Muhammad N, Lee HM, Kim J. Oncology therapeutics targeting the metabolism of amino acids. Cells. 2020;9(8):1904.
Article CAS PubMed PubMed Central Google Scholar
Karimi N, Moghaddam SJ. KRAS-mutant lung cancer: targeting molecular and immunologic pathways, therapeutic advantages and restrictions. Cells. 2023;12(5):749.
Article CAS PubMed PubMed Central Google Scholar
Rodak O, Peris-Díaz MD, Olbromski M, Podhorska-Okołów M, Dzięgiel P. Current landscape of non-small cell lung cancer: epidemiology, histological classification, targeted therapies, and immunotherapy. Cancers (Basel). 2021;13(18):4705.
Article CAS PubMed Google Scholar
Zheng S, Bian H, Li J, Shen Y, Yang Y, Hu W. Differentiation therapy: Unlocking phenotypic plasticity of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2022;180:103854.
Article PubMed Google Scholar
Roger E, Gout J, Arnold F, Beutel AK, Müller M, Abaei A, et al. Maintenance therapy for ATM-deficient pancreatic cancer by multiple DNA damage response interferences after platinum-based chemotherapy. Cells. 2020;9(9):2110.
Article CAS PubMed PubMed Central Google Scholar
Scaravilli M, Koivukoski S, Latonen L. Androgen-driven fusion genes and chimeric transcripts in prostate cancer. Front Cell Dev Biol. 2021;9: 623809.
Article PubMed PubMed Central Google Scholar
Ediriweera MK, Tennekoon KH, Samarakoon SR. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: biological and therapeutic significance. Semin Cancer Biol. 2019;59:147–60.
Article CAS PubMed Google Scholar
Brown WS, McDonald PC, Nemirovsky O, Awrey S, Chafe SC, Schaeffer DF, et al. Overcoming adaptive resistance to KRAS and MEK inhibitors by Co-targeting mTORC1/2 complexes in pancreatic cancer. Cell Reports Med. 2020;1: 100131.
Article CAS Google Scholar
D’Amato V, Raimondo L, Formisano L, Giuliano M, De Placido S, Rosa R, et al. Mechanisms of lapatinib resistance in HER2-driven breast cancer. Cancer Treat Rev. 2015;41:877–83.
Article PubMed Google Scholar
Di Lorenzo G, Buonerba C, de Placido S. Rapidly progressive disease in a castration-resistant prostate cancer patient after cabazitaxel discontinuation. Anticancer Drugs. 2015;26:236–9.
Article PubMed Google Scholar
Jacobs SA, Lee JJ, George TJ, Wade JL III, Stella PJ, Wang D, et al. Neratinib-plus-cetuximab in quadruple-WT (KRAS, NRAS, BRAF, PIK3CA) metastatic colorectal cancer resistant to cetuximab or panitumumab: NSABP FC-7, A Phase Ib Study. Clin Cancer Res. 2021;27:1612–22.
Article CAS PubMed Google Scholar
Hong JY, Cho HJ, Sa JK, Liu X, Ha SY, Lee T, et al. Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial. Genome Med. 2022;14:1.
Article CAS PubMed PubMed Central Google Scholar
Portier L, Desterke C, Chaker D, Oudrhiri N, Asgarova A, Dkhissi F, et al. iPSC-derived hereditary breast cancer model reveals the BRCA1-deleted tumor niche as a new culprit in disease progression. Int J Mol Sci. 2021;22:1227.
Article CAS PubMed PubMed Central Google Scholar
Zhao Q, Hai B, Zhang X, Xu J, Koehler B, Liu F. Biomimetic nanovesicles made from iPS cell-derived mesenchymal stem cells for targeted therapy of triple-negative breast cancer. Nanomedicine. 2020;24: 102146.
Article CAS PubMed Google Scholar
Chao H-M, Chern E. Patient-derived induced pluripotent stem cells for models of cancer and cancer stem cell research. J Formos Med Assoc. 2018;117:1046–57.
Article PubMed Google Scholar
Hundt M, Li M, Huang H, Obejero-Paz C, Bove P, Hernandez I, et al. 775 An induced pluripotent stem cell (iPSC) vaccine decreases tumor growth and improves survival in a therapeutic mouse model of colon cancer. J Immunother Cancer. 2021;9:A810–A810.
Article Google Scholar
Zhao Q, Hai B, Kelly J, Wu S, Liu F. Extracellular vesicle mimics made from iPS cell-derived mesenchymal stem cells improve the treatment of metastatic prostate cancer. Stem Cell Res Ther. 2021;12:29.
Article CAS PubMed PubMed Central Google Scholar
Chen Y, Zheng YL, Qiu DB, Sun YP, Kuang SJ, Xu Y, et al. An extracellular matrix culture system for induced pluripotent stem cells derived from human dental pulp cells. Eur Rev Med Pharmacol Sci. 2015;19:4035–46.
CAS PubMed Google Scholar
Liu R, Qian K, Xiao Y, Jiang W. Generation of two induced pluripotent stem cell lines from blood cells of a prostate cancer patient carrying germline mutation in CHEK2. Stem Cell Res. 2021;53: 102299.
Article CAS PubMed Google Scholar
Hepburn AC, Curry EL, Moad M, Steele RE, Franco OE, Wilson L, et al. Propagation of human prostate tissue from induced pluripotent stem cells. Stem Cells Transl Med. 2020;9:734–45.
Article PubMed PubMed Central Google Scholar
Welte Y, Davies C, Schäfer R, Regenbrecht CRA. Patient derived cell culture and isolation of CD133+ putative cancer stem cells from melanoma. J Vis Exp. 2013;13(73):e50200.
Itoh M, Kawagoe S, Okano HJ, Nakagawa H. 228 Generation of induced pluripotent stem cells (iPSCs) from NY-ESO-1-specific CD8+ T cell isolated from the patient with melanoma. J Invest Dermatol. 2017;137:S231.
Article Google Scholar
Castro-Pérez E, Sadangi S, Singh M, Setaluri V. Melanoma-derived induced pluripotent stem cells: a model for understanding melanoma cell of origin and drug resistance. Cell Sources iPSCs. 2021;191–219.
Kumano K, Arai S, Hosoi M, Taoka K, Takayama N, Otsu M, et al. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood J Am Soc Hematol. 2012;119(26):6234–42.
Wehbe Z, Ghanjati F, Flotho C. Induced pluripotent stem cells to model juvenile myelomonocytic leukemia: New perspectives for preclinical research. Cells. 2021;10:2335.
Article CAS PubMed PubMed Central Google Scholar
Turhan A, Foudi A, Hwang JW, Desterke C, Griscelli F, Bennaceur-Griscelli A. Modeling malignancies using induced pluripotent stem cells: from chronic myeloid leukemia to hereditary cancers. Exp Hematol. 2019;71:61–7.
Article CAS PubMed Google Scholar
Imeri J, Desterke C, Marcoux P, Telliam G, Sanekli S, Barreau S, et al. Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs). Cells. 2023;12:598.
Article CAS PubMed PubMed Central Google Scholar
Baliña-Sánchez C, Aguilera Y, Adan N, Sierra-Párraga JM, Olmedo-Moreno L, Panadero-Morón C, et al. Generation of mesenchymal stromal cells from urine-derived iPSCs of pediatric brain tumor patients. Front Immunol. 2023;14:1022676.
Article PubMed PubMed Central Google Scholar
Khamis ZI, Sarker DB, Xue Y, Al-Akkary N, James VD, Zeng C, et al. Modeling human brain tumors and the microenvironment using induced pluripotent stem cells. Cancers (Basel). 2023;15:1253.
Article CAS PubMed Google Scholar
Grigore F-N, Yang SJ, Chen CC, Koga T. Pioneering models of pediatric brain tumors. Neoplasia. 2023;36: 100859.
Article CAS PubMed PubMed Central Google Scholar
Bindhya S, Sidhanth C, Krishnapriya S, Garg M, Ganesan TS. Development and in vitro characterisation of an induced pluripotent stem cell model of ovarian cancer. Int J Biochem Cell Biol. 2021;138: 106051.
Article CAS PubMed Google Scholar
Lubbers JM, van Rooij N, Broekhuis MJC, Huizinga EGC, Warmerdam DO, Foijer F, et al. Urine-derived ovarian cancer patient iPSC as novel tool to study cancer immunotherapy. Genotypic phenotypic Determ Immun. 2022;129.
Fan H, Atiya HI, Wang Y, Pisanic TR, Wang T-H, Shih I-M, et al. Epigenomic reprogramming toward mesenchymal-epithelial transition in ovarian-cancer-associated mesenchymal stem cells drives metastasis. Cell Rep. 2020;33: 108473.
Article CAS PubMed PubMed Central Google Scholar
Ouyang X, Liu Y, Zhou Y, Guo J, Wei T-T, Liu C, et al. Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer. Stem cell reports. 2021;16:1468–77.
Article CAS PubMed PubMed Central Google Scholar
Kim J, Hoffman JP, Alpaugh RK, Rhim AD, Reichert M, Stanger BZ, et al. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep. 2013;3:2088–99.
Article CAS PubMed PubMed Central Google Scholar
Herreros-Villanueva M, Bujanda L, Billadeau DD, Zhang J-S. Embryonic stem cell factors and pancreatic cancer. World J Gastroenterol WJG. 2014;20:2247.
Article CAS PubMed Google Scholar
Calle AS, Nair N, Oo AK, Prieto-Vila M, Koga M, Khayrani AC, et al. A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm). Am J Cancer Res. 2016;6:2799.
CAS PubMed PubMed Central Google Scholar
Ishii M, Ando J, Yamazaki S, Toyota T, Ohara K, Furukawa Y, et al. iPSC-Derived neoantigen-specific CTL therapy for Ewing SarcomaiPSC-derived neoantigen-specific CTLs for Ewing sarcoma. Cancer Immunol Res. 2021;9:1175–86.
Article CAS PubMed Google Scholar
Lin Y-H, Jewell BE, Gingold J, Lu L, Zhao R, Wang LL, et al. Osteosarcoma: molecular pathogenesis and iPSC modeling. Trends Mol Med. 2017;23:737–55.
Article CAS PubMed PubMed Central Google Scholar
Kim JJ. Applications of iPSCs in cancer research: supplementary issue: stem cell biology. Biomark Insights. 2015;10:BMI-S20065.
Article Google Scholar
Wuputra K, Ku C-C, Kato K, Wu D-C, Saito S, Yokoyama KK. Translational models of 3-D organoids and cancer stem cells in gastric cancer research. Stem Cell Res Ther. 2021;12:1–16.
Article Google Scholar
Müller M, Hermann PC, Liebau S, Weidgang C, Seufferlein T, Kleger A, et al. The role of pluripotency factors to drive stemness in gastrointestinal cancer. Stem Cell Res. 2016;16:349–57.
Article PubMed Google Scholar
Lim KL, Teoh HK, Choong PF, Teh HX, Cheong SK, Kamarul T. Reprogramming cancer cells: overview & current progress. Expert Opin Biol Ther. 2016;16:941–51.
Article PubMed Google Scholar
Li Y-R, Dunn ZS, Zhou Y, Lee D, Yang L. Development of stem cell-derived immune cells for off-the-Shelf cancer immunotherapies. Cells. 2021;10:3497.
Article CAS PubMed PubMed Central Google Scholar
Borges L, Wallet MA, Bullaughey C-L, Naso MF, Gurung B, Keating S, et al. Development of multi-engineered ipsc-derived car-nk cells for the treatment of b-cell malignancies. Blood. 2021;138:1729.
Article Google Scholar
Afify SM, Sanchez Calle A, Hassan G, Kumon K, Nawara HM, Zahra MH, et al. A novel model of liver cancer stem cells developed from induced pluripotent stem cells. Br J Cancer. 2020;122:1378–90.
Article PubMed PubMed Central Google Scholar
Wuputra K, Lin C-S, Tsai M-H, Ku C-C, Lin W-H, Yang Y-H, et al. Cancer cell reprogramming to identify the genes competent for generating liver cancer stem cells. Inflamm Regen. 2017;37:1–7.
Article Google Scholar
Yu Y, Wang X, Nyberg SL. Application of induced pluripotent stem cells in liver diseases. Cell Med. 2014;7:1–13.
Article CAS PubMed PubMed Central Google Scholar
Palechor-Ceron N, Krawczyk E, Dakic A, Simic V, Yuan H, Blancato J, et al. Conditional reprogramming for patient-derived cancer models and next-generation living biobanks. Cells. 2019;8:1327.
Article CAS PubMed PubMed Central Google Scholar
Iskender B, Izgi K, Canatan H. Reprogramming bladder cancer cells for studying cancer initiation and progression. Tumor Biol. 2016;37:13237–45.
Article CAS Google Scholar
Qin D, Long T, Deng J, Zhang Y. Urine-derived stem cells for potential use in bladder repair. Stem Cell Res Ther. 2014;5:1–10.
Article Google Scholar
Raad S, David A, Sagniez M, Paré B, Orfi Z, Dumont NA, et al. iPSCs derived from esophageal atresia patients reveal SOX2 dysregulation at the anterior foregut stage. Dis Model Mech. 2022;15:dmm049541.
Article CAS PubMed PubMed Central Google Scholar
Wang H, Wang R, Prothro KP, Xi S, Hou W, Wu X, et al. Abstract A013: Induced pluripotent stem cells derived from normal human esophageal epithelial cells identify transcription factor networks contributing to esophageal carcinogenesis. Cancer Res. 2022;82:A013–A013.
Article Google Scholar
Liang F, Xu H, Cheng H, Zhao Y, Zhang J-H. Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer. Authorea Prepr. 2023.
Tu J, Huo Z, Yu Y, Zhu D, Xu A, Huang M-F, et al. Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies. Proc Natl Acad Sci. 2022;119: e2117857119.
Article CAS PubMed PubMed Central Google Scholar
Yamasaki AE, King NE, Matsui H, Jepsen K, Panopoulos AD. Two iPSC lines generated from the bone marrow of a relapsed/refractory AML patient display normal karyotypes and myeloid differentiation potential. Stem Cell Res. 2019;41: 101587.
Article CAS PubMed Google Scholar
Bauer D. Studying tumor-derived and induced pluripotent stem cell-derived organoids for kidney cancer research. 2022.
Google Scholar
de Carvalho Ribeiro P, Oliveira LF, Caldas HC. Differentiating induced pluripotent stem cells into renal cells: a new approach to treat kidney diseases. Stem Cells Int. 2020;2020:8894590.
Google Scholar
Li Q, Tian S, Guo Y, Niu X, Hu B, Guo S, et al. Transplantation of induced pluripotent stem cell-derived renal stem cells improved acute kidney injury. Cell Biosci. 2015;5:1–9.
Article Google Scholar
Montserrat N, Ramírez-Bajo MJ, Xia Y, Sancho-Martinez I, Moya-Rull D, Miquel-Serra L, et al. Generation of induced pluripotent stem cells from human renal proximal tubular cells with only two transcription factors, OCT4 and SOX2. J Biol Chem. 2012;287:24131–8.
Article CAS PubMed PubMed Central Google Scholar
Kaminski MM, Tosic J, Kresbach C, Engel H, Klockenbusch J, Müller A-L, et al. Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. Nat Cell Biol. 2016;18:1269–80.
Article CAS PubMed Google Scholar
Kenter AT, Rentmeester E, Riet J, Boers R, Boers J, Ghazvini M, et al. Cystic renal-epithelial derived induced pluripotent stem cells from polycystic kidney disease patients. Stem Cells Transl Med. 2020;9:478–90.
Article CAS PubMed PubMed Central Google Scholar
Sewell W, Lin R-Y. Generation of thyroid follicular cells from pluripotent stem cells: potential for regenerative medicine. Front Endocrinol (Lausanne). 2014;5:96.
Article PubMed Google Scholar
Abu-Bonsrah KD, Newgreen DF, Dottori M. Development of functional thyroid C cell-like cells from human pluripotent cells in 2D and in 3D scaffolds. Cells. 2021;10:2897.
Article CAS PubMed PubMed Central Google Scholar
Mei W, Lin X, Kapoor A, Gu Y, Zhao K, Tang D. The contributions of prostate cancer stem cells in prostate cancer initiation and metastasis. Cancers (Basel). 2019;11:434.
Article CAS PubMed Google Scholar
Buskin A, Singh P, Lorenz O, Robson C, Strand DW, Heer R. A review of prostate organogenesis and a role for iPSC-derived prostate organoids to study prostate development and disease. Int J Mol Sci. 2021;22(23):13097.
Article CAS PubMed PubMed Central Google Scholar
Setaluri V. Differentiation of neonatal human-induced pluripotent stem cells to prostate epithelial cells: a model to study prostate cancer development. New York: Wisconsin Univ Madison; 2013.
Gandre-Babbe S, Paluru P, Aribeana C, Chou ST, Bresolin S, Lu L, et al. Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia. Blood, J Am Soc Hematol. 2013;121:4925–9.
CAS Google Scholar
Li T, Zhang Y, Li Y, Wang X, Bao W, Huang J, et al. Modeling leukemia with pediatric acute leukemia patient-derived iPSCs. Stem Cell Res. 2021;54: 102404.
Article CAS PubMed Google Scholar
Miyauchi M, Koya J, Arai S, Yamazaki S, Honda A, Kataoka K, et al. ADAM8 is an antigen of tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells identified by patient-derived induced pluripotent stem cells. Stem cell reports. 2018;10:1115–30.
Article CAS PubMed PubMed Central Google Scholar
Lee S-J, Kim J-H, Kang K-W, Lee B-H, Kim B-S. Generation of normal induced pluripotent stem cell line KUMCi002-A from bone marrow CD34+ cells of patient with multiple myeloma disease having 13q deletion and IGH translocation. Stem Cell Res. 2020;49: 102030.
Article CAS PubMed Google Scholar
Kim J-H, Hong J-H, Kang K-W, Lee B-H, Park Y, Kim B-S. Generation of the human pluripotent stem cell lines KUMi005-A from a patients with multiple myeloma. Stem Cell Res. 2022;65: 102939.
Article CAS PubMed Google Scholar
Utikal J, Maherali N, Kulalert W, Hochedlinger K. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci. 2009;122:3502–10.
Article CAS PubMed PubMed Central Google Scholar
Osborn MJ, Newby GA, McElroy AN, Knipping F, Nielsen SC, Riddle MJ, et al. Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and iPSCs. J Invest Dermatol. 2020;140:338–47.
Article CAS PubMed Google Scholar
Ohnishi H, Kawasaki T, Deguchi T, Yuba S. Generation of xeroderma pigmentosum-a patient-derived induced pluripotent stem cell line for use as future disease model. Cell Reprogram (Formerly“ Cloning Stem Cells”). 2015;17:268–74.
CAS Google Scholar
Barczak W, Golusiński P, Luczewski L, Suchorska WM, Masternak MM, Golusiński W. The importance of stem cell engineering in head and neck oncology. Biotechnol Lett. 2016;38:1665–72.
Article CAS PubMed PubMed Central Google Scholar
Koh SP, Brasch HD, de Jongh J, Itinteang T, Tan ST. Cancer stem cell subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma. Heliyon. 2019;5: e02257.
Article PubMed PubMed Central Google Scholar
Wang G, Heimendinger P, Ramelmeier RA, Wang W. Pluripotent stem cell-based cell therapies: Current applications and future prospects. Curr Opin Biomed Eng. 2022;22:100390.
Article CAS Google Scholar
Saito S, Lin Y-C, Nakamura Y, Eckner R, Wuputra K, Kuo K-K, et al. Potential application of cell reprogramming techniques for cancer research. Cell Mol Life Sci. 2019;76:45–65.
Article CAS PubMed Google Scholar
Choi J, Curtis SJ, Roy DM, Flesken-Nikitin A, Nikitin AY. Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency. Am J Pathol. 2010;177:2645–58.
Article CAS PubMed PubMed Central Google Scholar
Genadry KC, Pietrobono S, Rota R, Linardic CM. Soft tissue sarcoma cancer stem cells: an overview. Front Oncol. 2018;8:475.
Article PubMed PubMed Central Google Scholar
Pang LK, Pena M, Zhao R, Lee D-F. Modeling of osteosarcoma with induced pluripotent stem cells. Stem Cell Res. 2020;49: 102006.
Article CAS PubMed Google Scholar
Sanjurjo-Rodríguez C, Castro-Viñuelas R, Piñeiro-Ramil M, Rodríguez-Fernández S, Fuentes-Boquete I, Blanco FJ, et al. Versatility of induced pluripotent stem cells (iPSCs) for improving the knowledge on musculoskeletal diseases. Int J Mol Sci. 2020;21:6124.
Article PubMed PubMed Central Google Scholar
Cefalo MG, Carai A, Miele E, Po A, Ferretti E, Mastronuzzi A, et al. Human iPSC for therapeutic approaches to the nervous system: present and future applications. Stem Cells Int. 2016;2016:4869071.
Article PubMed Google Scholar
Emdad L, D’Souza SL, Kothari HP, Qadeer ZA, Germano IM. Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes. Stem Cells Dev. 2012;21:404–10.
Article CAS PubMed Google Scholar
Zhou L, Li P, Chen N, Dai L, Gao K, Liu Y, et al. Modeling vanishing white matter disease with patient-derived induced pluripotent stem cells reveals astrocytic dysfunction. CNS Neurosci Ther. 2019;25:759–71.
Article CAS PubMed PubMed Central Google Scholar
Juopperi TA, Kim WR, Chiang C-H, Yu H, Margolis RL, Ross CA, et al. Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington’s disease patient cells. Mol Brain. 2012;5:1–14.
Article Google Scholar
Ladran I, Tran N, Topol A, Brennand KJ. Neural stem and progenitor cells in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2013;5:701–15.
Article CAS PubMed PubMed Central Google Scholar
Curry EL, Moad M, Robson CN, Heer R. Using induced pluripotent stem cells as a tool for modelling carcinogenesis. World J Stem Cells. 2015;7:461.
Article PubMed PubMed Central Google Scholar
Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, et al. Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): a new approach to finding targets for cervical cancer stem cell treatment. Oncotarget. 2017;8:40935.
Article PubMed PubMed Central Google Scholar
Huang Y-P, Liu K, Wang Y-X, Yang Y, Xiong L, Zhang Z-J, et al. Application and research progress of organoids in cholangiocarcinoma and gallbladder carcinoma. Am J Cancer Res. 2021;11:31.
CAS PubMed PubMed Central Google Scholar
Leslie JL, Young VB. A whole new ball game: Stem cell-derived epithelia in the study of host–microbe interactions. Anaerobe. 2016;37:25–8.
Article PubMed Google Scholar
Cheng L, Albers P, Berney DM, Feldman DR, Daugaard G, Gilligan T, et al. Testicular cancer. Nat Rev Dis Prim. 2018;4:29.
Article PubMed Google Scholar
Biswal BK, Beyrouthy MJ, Hever-Jardine MP, Armstrong D, Tomlinson CR, Christensen BC, et al. Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS ONE. 2012;7: e53003.
Article CAS PubMed PubMed Central Google Scholar
Laronda MM, Burdette JE, Kim JJ, Woodruff TK. Recreating the female reproductive tract in vitro using iPSC technology in a linked microfluidics environment. Stem Cell Res Ther. 2013;4:1–5.
Article Google Scholar
Miyazaki K, Dyson MT, Furukawa Y, Yilmaz BD, Maruyama T, Bulun SE. Generation of progesterone-responsive endometrial stromal fibroblasts from human induced pluripotent stem cells: role of the WNT/CTNNB1 pathway. Stem Cell Reports. 2018;11:1136–55.
Article CAS PubMed PubMed Central Google Scholar
Başaran İY, Karaöz E. Generation of induced pluripotent stem cells from patients with multiple myeloma. Turkish J Hematol. 2021;38:254.
Google Scholar
Tian L, Ye Z, Kafka K, Stewart D, Anders R, Schwarz KB, et al. Biliary atresia relevant human induced pluripotent stem cells recapitulate key disease features in a dish. J Pediatr Gastroenterol Nutr. 2019;68:56.
Article PubMed Google Scholar
Jalan-Sakrikar N, De Assuncao TM, Navarro-Corcuera A, Hamdan FH, Loarca L, Kirkeby LA, et al. Induced pluripotent stem cells from subjects with primary sclerosing cholangitis develop a senescence phenotype following biliary differentiation. Hepatol Commun. 2022;6:345–60.
Article CAS PubMed Google Scholar
Moad M, Pal D, Hepburn AC, Williamson SC, Wilson L, Lako M, et al. A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells. Eur Urol. 2013;64:753–61.
Article PubMed PubMed Central Google Scholar
Hwang JW, Loisel-Duwattez J, Desterke C, Latsis T, Pagliaro S, Griscelli F, et al. A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC). Biochim Biophys Acta Gen Subj. 2020;1864:129540.
Article CAS PubMed Google Scholar
Kim E, Kim M, Hwang S, Kim J, Lee G, Park YS, et al. Neural induction of porcine-induced pluripotent stem cells and further differentiation using glioblastoma-cultured medium. J Cell Mol Med. 2019;23:2052–63.
Article CAS PubMed PubMed Central Google Scholar
Ahmed N, Escalona R, Leung D, Chan E, Kannourakis G. Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells: perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells. Semin Cancer Biol. 2018;53:265–81.
Article CAS PubMed Google Scholar
Bresnahan E, Ramadori P, Heikenwalder M, Zender L, Lujambio A. Novel patient-derived preclinical models of liver cancer. J Hepatol. 2020;72:239–49.
Article CAS PubMed Google Scholar
Alexanova A, Raitoharju E, Valtonen J, Aalto-Setälä K, Viiri LE. Coronary artery disease patient-derived iPSC-hepatocytes have distinct miRNA profile that may alter lipid metabolism. Sci Rep. 2023;13:1706.
Article CAS PubMed PubMed Central Google Scholar
Ng NHJ, Jasmen JB, Lim CS, Lau HH, Krishnan VG, Kadiwala J, et al. HNF4A haploinsufficiency in MODY1 abrogates liver and pancreas differentiation from patient-derived induced pluripotent stem cells. Iscience. 2019;16:192–205.
Article CAS PubMed PubMed Central Google Scholar
Suva M-L, Riggi N, Stehle J-C, Baumer K, Tercier S, Joseph J-M, et al. Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res. 2009;69:1776–81.
Article CAS PubMed Google Scholar
Todorova R. Ewing’s sarcoma cancer stem cell targeted therapy. Curr Stem Cell Res Ther. 2014;9:46–62.
Article CAS PubMed Google Scholar
Zeng S, Liu L, Ouyang Q, Zhao Y, Lin G, Hu L, et al. Generation of induced pluripotent stem cells (iPSCs) from a retinoblastoma patient carrying a c. 2663G> A mutation in RB1 gene. Stem Cell Res. 2016;17:208–11.
Article CAS PubMed Google Scholar
Ou A, Zhao X, Lu Z. The potential roles of p53 signaling reactivation in pancreatic cancer therapy. Biochim Biophys Acta Rev Cancer. 2022;1877:188662.
Article CAS PubMed Google Scholar
Shen Y-A, Wang C-Y, Hsieh Y-T, Chen Y-J, Wei Y-H. Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma. Cell Cycle. 2015;14:86–98.
Article PubMed Google Scholar
Shen Y-A, Lin C-H, Chi W-H, Wang C-Y, Hsieh Y-T, Wei Y-H, et al. Resveratrol impedes the stemness, epithelial-mesenchymal transition, and metabolic reprogramming of cancer stem cells in nasopharyngeal carcinoma through p53 activation. Evid Based Complement Alternat Med. 2013;2013:590393.
Article PubMed PubMed Central Google Scholar
Shen Y-A, Wang C-Y, Chuang H-Y, Hwang JJ-J, Chi W-H, Shu C-H, et al. CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation. Oncotarget. 2016;7:58351–66.
Article PubMed PubMed Central Google Scholar
Lichner Z, Mac-Way F, Yousef GM. Obstacles in renal regenerative medicine: metabolic and epigenetic parallels between cellular reprogramming and kidney cancer oncogenesis. Eur Urol Focus. 2019;5:250–61.
Article PubMed Google Scholar
O’Neill AC, Ricardo SD. Human kidney cell reprogramming: applications for disease modeling and personalized medicine. J Am Soc Nephrol. 2013;24:1347–56.
Article PubMed PubMed Central Google Scholar
Oosterhuis JW, Looijenga LHJ. Human germ cell tumours from a developmental perspective. Nat Rev Cancer. 2019;19:522–37.
Article CAS PubMed Google Scholar
Yang S, Ding S, He S, He L, Gao K, Peng S, et al. Differentiation of primordial germ cells from premature ovarian insufficiency-derived induced pluripotent stem cells. Stem Cell Res Ther. 2019;10:1–11.
Article Google Scholar
Niemitz E. Isogenic iPSC-derived models of disease. Nat Genet. 2014;46:7.
Article CAS Google Scholar
Ahn H-S, Ryu J-S, Lee J, Mun SJ, Hong Y-H, Shin Y, et al. Generation of An Induced Pluripotent Stem Cell Line from Human Liver Fibroblasts from A Patient with Combined Hepatocellular-Cholangiocarcinoma. Cell J. 2022;24:133.
PubMed PubMed Central Google Scholar
Pandian V, Ramraj S, Khan FH, Azim T, Aravindan N. Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling. Stem Cell Res Ther. 2015;6:1–13.
Article CAS Google Scholar
Tucker ER, George S, Angelini P, Bruna A, Chesler L. The promise of patient-derived preclinical models to accelerate the implementation of personalised medicine for children with neuroblastoma. J Pers Med. 2021;11:248.
Article PubMed PubMed Central Google Scholar
Zeleniak A, Wiegand C, Liu W, McCormick C, Alavi A, Guan H, et al. De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids. Nat Methods. 2022;19:1306–19.
Article CAS PubMed Google Scholar
Vizcardo R, Klemen ND, Islam SMR, Gurusamy D, Tamaoki N, Yamada D, et al. Generation of tumor antigen-specific iPSC-derived thymic emigrants using a 3D thymic culture system. Cell Rep. 2018;22:3175–90.
Article CAS PubMed PubMed Central Google Scholar
Kervarrec T, Samimi M, Guyétant S, Sarma B, Chéret J, Blanchard E, et al. Histogenesis of Merkel cell carcinoma: a comprehensive review. Front Oncol. 2019;9:451.
Article PubMed PubMed Central Google Scholar
Van Geest FS, Meima ME, Stuurman KE, Wolf NI, Van Der Knaap MS, Lorea CF, et al. Clinical and functional consequences of C-terminal variants in MCT8: a case series. J Clin Endocrinol Metab. 2021;106:539–53.
Article PubMed Google Scholar
Morey R, Bui T, Fisch KM, Horii M. Modeling placental development and disease using human pluripotent stem cells. Placenta. 2022;141:18–25.
Article PubMed PubMed Central Google Scholar
Horii M, Li Y, Wakeland AK, Pizzo DP, Nelson KK, Sabatini K, et al. Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease. Proc Natl Acad Sci. 2016;113:E3882–91.
Article CAS PubMed PubMed Central Google Scholar
Papathomas TG, Sun N, Chortis V, Taylor AE, Arlt W, Richter S, et al. Novel methods in adrenal research: a metabolomics approach. Histochem Cell Biol. 2019;151:201–16.
Article CAS PubMed Google Scholar
Naiki Y, Miyado M, Shindo M, Horikawa R, Hasegawa Y, Katsumata N, et al. Adeno-associated virus-mediated gene therapy for patients’ fibroblasts, induced pluripotent stem cells, and a mouse model of congenital adrenal hyperplasia. Hum Gene Ther. 2022;33:801–9.
Article CAS PubMed Google Scholar
Ong SLM, Szuhai K, Bovée JVMG. Gene fusions in vascular tumors and their underlying molecular mechanisms. Expert Rev Mol Diagn. 2021;21:897–909.
Article CAS PubMed Google Scholar
Martins-Neves SR, Sampaio-Ribeiro G, Gomes CMF. Self-renewal and pluripotency in osteosarcoma stem cells’ chemoresistance: notch, hedgehog, and Wnt/β-Catenin interplay with embryonic markers. Int J Mol Sci. 2023;24:8401.
Article CAS PubMed PubMed Central Google Scholar
Wang H, Du Y-C, Zhou X, Liu H, Tang S-C. The dual functions of YAP-1 to promote and inhibit cell growth in human malignancy. Cancer Metastasis Rev. 2014;33:173–81.
Article CAS PubMed Google Scholar
Yang S, Hu H, Kung H, Zou R, Dai Y, Hu Y, et al. Organoids: The current status and biomedical applications. MedComm. 2023;4: e274.
Article CAS PubMed PubMed Central Google Scholar
Abbott DM, Bortolotto C, Benvenuti S, Lancia A, Filippi AR, Stella GM. Malignant pleural mesothelioma: genetic and microenviromental heterogeneity as an unexpected reading frame and therapeutic challenge. Cancers (Basel). 2020;12:1186.
Article CAS PubMed Google Scholar
McLoughlin KC, Kaufman AS, Schrump DS. Targeting the epigenome in malignant pleural mesothelioma. Transl lung cancer Res. 2017;6:350.
Article CAS PubMed PubMed Central Google Scholar
Hadoux J, Desterke C, Féraud O, Guibert M, De Rose RF, Opolon P, et al. Generation of patient-specific and genome-edited MEN2A patient-derived induced pluripotent stem cells as novel tools for drug screening. Cancer Res. 2016;76:2483.
Article Google Scholar
Shukla V, Rao M, Zhang H, Beers J, Wangsa D, Wangsa D, et al. ASXL3 is a novel pluripotency factor in human respiratory epithelial cells and a potential therapeutic target in small cell lung CancerASXL3, Lu-iPSC, and SCLC. Cancer Res. 2017;77:6267–81.
Article CAS PubMed PubMed Central Google Scholar
Wang F, Yang M, Luo W, Zhou Q. Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer. J Natl Cancer Cent. 2022;20.
Hillger JM, Lieuw W-L, Heitman LH, Ijzerman AP. Label-free technology and patient cells: from early drug development to precision medicine. Drug Discov Today. 2017;22:1808–15.
Article CAS PubMed Google Scholar
Gaebler M, Silvestri A, Haybaeck J, Reichardt P, Lowery CD, Stancato LF, et al. Three-dimensional patient-derived in vitro sarcoma models: promising tools for improving clinical tumor management. Front Oncol. 2017;7:203.
Article PubMed PubMed Central Google Scholar
Adkar SS, Brunger JM, Willard VP, Wu C-L, Gersbach CA, Guilak F. Genome engineering for personalized arthritis therapeutics. Trends Mol Med. 2017;23:917–31.
Article CAS PubMed PubMed Central Google Scholar
Sun Q, Shen Z, Liang X, He Y, Kong D, Midgley AC, et al. Progress and current limitations of materials for artificial bile duct engineering. Materials (Basel). 2021;14:7468.
Article CAS PubMed Google Scholar
Li J, Hou S, Ye Z, Wang W, Hu X, Hang Q. Long non-coding RNAs in pancreatic cancer: biologic functions, mechanisms, and clinical significance. Cancers (Basel). 2022;14:2115.
Article CAS PubMed Google Scholar
Rocchi C, Emmerson E. Mouth-watering results: Clinical need, current approaches, and future directions for salivary gland regeneration. Trends Mol Med. 2020;26:649–69.
Article PubMed Google Scholar
Boon N, Lu X, Andriessen CA, Moustakas I, Buck TM, Freund C, et al. AAV-mediated gene augmentation therapy of CRB1 patient-derived retinal organoids restores the histological and transcriptional retinal phenotype. Stem Cell Reports. 2023;18:1123–37.
Article CAS PubMed PubMed Central Google Scholar
Akter F, Simon B, de Boer NL, Redjal N, Wakimoto H, Shah K. Pre-clinical tumor models of primary brain tumors: challenges and opportunities. Biochim Biophys Acta Rev Cancer. 2021;1875:188458.
Article CAS PubMed Google Scholar
Nikitina TV, Lebedev IN. Stem cell-based trophoblast models to unravel the genetic causes of human miscarriages. Cells. 2022;11:1923.
Article PubMed PubMed Central Google Scholar
Cai J, Peng T, Wang J, Zhang J, Hu H, Tang D, et al. Isolation, culture and identification of choriocarcinoma stem-like cells from the human choriocarcinoma cell-line JEG-3. Cell Physiol Biochem. 2016;39:1421–32.
Article PubMed Google Scholar
Yan T, Mizutani A, Chen L, Takaki M, Hiramoto Y, Matsuda S, et al. Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles. J Cancer. 2014;5:572.
Article CAS PubMed PubMed Central Google Scholar
Lee H, Jo EB, Yang HM, Oh H, Park H, Shin S, et al. Patient-derived xenograft of de-differentiated liposarcoma for personalized treatment. 한국실험동물학회 학술발표대회 논문집. 2016;167.
Lõhmussaar K, Boretto M, Clevers H. Human-derived model systems in gynecological cancer research. Trends Cancer. 2020;6:1031–43.
Article PubMed Google Scholar
Stroncek DF, Berger C, Cheever MA, Childs RW, Dudley ME, Flynn P, et al. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer. J Transl Med. 2012;10:1–5.
Article Google Scholar
Maali A, Atashi A, Ghaffari S, Kouchaki R, Abdolmaleki F, Azad M. A review on leukemia and iPSC technology: application in novel treatment and future. Curr Stem Cell Res Ther. 2018;13:665–75.
Article CAS PubMed Google Scholar
Kim J-H, Kang K-W, Lee B-H, Park Y, Sung HJ, Kim B-S. A human pluripotent stem cell line KUMi004-A generated from a patient with chronic lymphocytic leukemia. Stem Cell Res. 2022;60: 102668.
Article CAS PubMed Google Scholar
Reid JC, Golubeva D, Boyd AL, Hollands CG, Henly C, Orlando L, et al. Human pluripotent stem cells identify molecular targets of trisomy 12 in chronic lymphocytic leukemia patients. Cell Rep. 2021;34: 108845.
Article CAS PubMed Google Scholar
Raghav Y, Dilliott AA, Petrozziello T, Kim SE, Berry JD, Cudkowicz ME, et al. Identification of gene fusions associated with amyotrophic lateral sclerosis. medRxiv. 2022;2006–22.
Seetharaman R, Mahmood A, Kshatriya P, Patel D, Srivastava A. An overview on stem cells in tissue regeneration. Curr Pharm Des. 2019;25:2086–98.
Article CAS PubMed Google Scholar
Destouni A, Mourmoura E, Konteles V, Sfougataki E, Mertzanian A, Brantzos T, et al. Characterization of the mitochondrial genome landscape in induced MSCS (IMSCS) derived from OA and healthy donors. Osteoarthr Cartil. 2022;30:S420–1.
Article Google Scholar
Raad S, David A, Que J, Faure C. Genetic mouse models and induced pluripotent stem cells for studying tracheal-esophageal separation and esophageal development. Stem Cells Dev. 2020;29:953–66.
Article CAS PubMed PubMed Central Google Scholar
Knappe N, Novak D, Weina K, Bernhardt M, Reith M, Larribere L, et al. Directed dedifferentiation using partial reprogramming induces invasive phenotype in melanoma cells. Stem Cells. 2016;34:832–46.
Article CAS PubMed Google Scholar
Li Y, Yang X, Plummer R, Hayashi Y, Deng X-S, Nie Y-Z, et al. Human pluripotent stem cell-derived hepatocyte-like cells and organoids for liver disease and therapy. Int J Mol Sci. 2021;22:10471.
Article CAS PubMed PubMed Central Google Scholar
Tian L, Deshmukh A, Prasad N, Jang Y-Y. Alcohol increases liver progenitor populations and induces disease phenotypes in human IPSC-derived mature stage hepatic cells. Int J Biol Sci. 2016;12:1052.
Article CAS PubMed PubMed Central Google Scholar
Hsu J, Reilly A, Hayes BJ, Clough CA, Konnick EQ, Torok-Storb B, et al. Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes. Blood J Am Soc Hematol. 2019;134:186–98.
CAS Google Scholar
Clough CA, Pangallo J, Sarchi M, Ilagan JO, North K, Bergantinos R, et al. Coordinated missplicing of TMEM14C and ABCB7 causes ring sideroblast formation in SF3B1-mutant myelodysplastic syndrome. Blood. 2022;139:2038–49.
Article CAS PubMed PubMed Central Google Scholar
Ochi T, Fujiwara T, Ono K, Suzuki C, Nikaido M, Inoue D, et al. Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome. Sci Rep. 2022;12:14562.
Article CAS PubMed PubMed Central Google Scholar
Gao J, Zhang B, Tang D, Gao T, Lin Q, Chu C, et al. Study on functional monoclonal antibodies of anti-human uterine sarcoma stem cell-like cells. 2020.
Google Scholar
Bleijs M, van de Wetering M, Clevers H, Drost J. Xenograft and organoid model systems in cancer research. EMBO J. 2019;38:e101654–e101654.
Article PubMed PubMed Central Google Scholar
Lu F, Ma XJ, Jin W-L, Luo Y, Li X. Neoantigen specific T cells derived from T cell-derived induced pluripotent stem cells for the treatment of hepatocellular carcinoma: potential and challenges. Front Immunol. 2021;12:690565.
Article CAS PubMed PubMed Central Google Scholar
Gras-Peña R, Danzl NM, Khosravi-Maharlooei M, Campbell SR, Ruiz AE, Parks CA, et al. Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus. J Allergy Clin Immunol. 2022;149:1755–71.
Article PubMed Google Scholar
Hosaka N, Kanda S, Shimono T, Nishiyama T. Induction of γδT cells from HSC-enriched BMCs co-cultured with iPSC-derived thymic epithelial cells. J Cell Mol Med. 2021;25:10604–13.
Article CAS PubMed PubMed Central Google Scholar
Milewski D, Tian M, Kim Y, Wei J, Khan J. Suppression of antigen presentation is a hallmark of pediatric rhabdomyosarcoma. Cancer Res. 2023;83:6736.
Article Google Scholar
Amir AA, Nouli KA, Sheikh SS. Benign prolapsing inflammatory rectal polyp with osseous metaplasia mimicking rhabdomyosarcoma botryioides. J Pediatr Surg Case Reports. 2020;56: 101297.
Article Google Scholar
Dehner CA, Armstrong AE, Yohe M, Shern JF, Hirbe AC. Genetic characterization, current model systems and prognostic stratification in PAX fusion-negative vs. PAX fusion-positive rhabdomyosarcoma. Genes (Basel). 2021;12:1500.
Article CAS PubMed Google Scholar
Huang M, Zheng T, Guo J, Sperring C, Miller M, McHenry L, et al. Human pluripotent stem cell-based models of neuroblastoma. Neuro Oncol. 2017;19:256.
Google Scholar
Ku C-C, Wuputra K, Pan J-B, Li C-P, Liu C-J, Liu Y-C, et al. Generation of human stomach cancer iPSC-derived organoids induced by helicobacter pylori infection and their application to gastric cancer research. Cells. 2022;11(2):184.
Article CAS PubMed PubMed Central Google Scholar
Kozurek E, Dickerson EB, Kim JH. Oncogenic PIK3CA promotes hematopoietic reprogramming and cell transdifferentiation developing hematopoietic malignancy. Cancer Res. 2023;83:2586.
Article Google Scholar
Wenthe S, Becklin K, Napiwocki B, Kozurek E, Moriarity B, Kim JH. Unveiling chromatin accessibility landscape and convergent oncogenic pathway in angiosarcoma models using induced pluripotent stem cells. Cancer Res. 2022;82:198.
Article Google Scholar
Kamada M, Kumazaki T, Matsuo T, Takahashi T, Mitsui Y. Yia-1 Generation of diverse malignant tumor cell lines from mouse fibroblast.
Tanaka Y, Sasaki T, Kulkeaw K, Tan KS, Yumine A, Swain A, et al. PS-1–1 Paracrine effects of CCL17 and CCL22 regulate hematopoietic stem cell migration in mouse fetal liver.
Lee D-F, Pereira C-F. Reprogramming Stars# 10: modeling cancer with cellular Reprogramming—an interview with Dr Dung-Fang Lee. Cell Reprogram. 2023;25:2–6.
Article CAS PubMed Google Scholar
Liu Z, Che P, Mercado JJ, Hackney JR, Friedman GK, Zhang C, et al. Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis. J Neurooncol. 2019;141:289–301.
Article CAS PubMed Google Scholar
Kovalenko TF, Yadav B, Anufrieva KS, Rubtsov YP, Zatsepin TS, Shcherbinina EY, et al. Functions of long non-coding RNA ROR in patient-derived glioblastoma cells. Biochimie. 2022;200:131–9.
Article CAS PubMed Google Scholar
Wlodarczyk A, Grot D, Stoczynska-Fidelus E, Rieske P. Gaps and doubts in search to recognize glioblastoma cellular origin and tumor initiating cells. J Oncol. 2020;2020:6783627.
Article PubMed PubMed Central Google Scholar
Suvà ML, Tirosh I. The glioma stem cell model in the era of single-cell genomics. Cancer Cell. 2020;37:630–6.
Article PubMed Google Scholar
Jha A. Tumor dedifferentiation: diagnostic and therapeutic implications. J Pathol Nepal. 2017;7:1202–11.
Article Google Scholar
Griscelli F, Oudrhiri N, Feraud O, Divers D, Portier L, Turhan AG, et al. Generation of induced pluripotent stem cell (iPSC) line from a patient with triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene. Stem Cell Res. 2017;24:135–8.
Article CAS PubMed Google Scholar
Sheyn D, Ben-David S, Tawackoli W, Zhou Z, Salehi K, Bez M, et al. Human iPSCs can be differentiated into notochordal cells that reduce intervertebral disc degeneration in a porcine model. Theranostics. 2019;9:7506.
Article CAS PubMed PubMed Central Google Scholar
Liu YJ, Silva F. Notochord-like cells derived from induced pluripotent stem cells and their therapeutic potential in treating sympathetic disc degeneration. In: Current Progress iPSC-derived Cell Types. London: Elsevier; 2021. p. 245–82.
Chen Y-Y, Wang W-H, Che L, Lan Y, Zhang L-Y, Zhan D-L, et al. BNIP3L-dependent mitophagy promotes HBx-induced cancer stemness of hepatocellular carcinoma cells via glycolysis metabolism reprogramming. Cancers (Basel). 2020;12:655.
Article CAS PubMed Google Scholar
Tafaleng EN, Chakraborty S, Han B, Hale P, Wu W, Soto-Gutierrez A, et al. Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency. Hepatology. 2015;62:147–57.
Article PubMed Google Scholar
Osborn SL, Thangappan R, Luria A, Lee JH, Nolta J, Kurzrock EA. Induction of human embryonic and induced pluripotent stem cells into urothelium. Stem Cells Transl Med. 2014;3:610–9.
Article CAS PubMed PubMed Central Google Scholar
Roussel MF, Stripay JL. Modeling pediatric medulloblastoma. Brain Pathol. 2020;30:703–12.
Article PubMed Google Scholar
Nagao K, Kato C, Ikemoto Y, Motojima T, Fujii K, Umezawa A, et al. PTCH1-null induced pluripotent stem cells exclusively differentiate into immature ectodermal cells with large areas of medulloblastoma-like tissue. Discov Oncol. 2022;13:36.
Article CAS PubMed PubMed Central Google Scholar
Karner C, Anders I, Vejzovic D, Szkandera J, Scheipl S, Deutsch AJA, et al. Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines. J Transl Med. 2023;21:54.
Article CAS PubMed PubMed Central Google Scholar
Pang LK, Huang M-F, Gingold JA, Pena M, Zhao R, Lee D-F. Progress and possibilities for patient-derived iPSCs and genetically engineered stem cells in cancer modeling and targeted therapies. iPSCs-State Sci. 2022;247–88.
Hwang JW, Desterke C, Féraud O, Richard S, Ferlicot S, Verkarre V, et al. IPSC-derived embryoid bodies as models of c-met-mutated hereditary papillary renal cell carcinoma. Int J Mol Sci. 2019;20:4867.
Article CAS PubMed PubMed Central Google Scholar
Nogales FF, Dulcey I, Preda O. Germ cell tumors of the ovary: an update. Arch Pathol Lab Med. 2014;138:351–62.
Article PubMed Google Scholar
Ikemoto Y, Takayama Y, Fujii K, Masuda M, Kato C, Hatsuse H, et al. Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome. J Med Genet. 2017;54:579–84.
Article CAS PubMed Google Scholar
Sellheyer K. Basal cell carcinoma: cell of origin, cancer stem cell hypothesis and stem cell markers. Br J Dermatol. 2011;164:696–711.
Article CAS PubMed Google Scholar
Kometani T, Kamo K, Kido T, Hiraoka N, Chibazakura T, Unno K, et al. Development of a novel co-culture system using human pancreatic cancer cells and human iPSC-derived stellate cells to mimic the characteristics of pancreatic ductal adenocarcinoma in vitro. Biochem Biophys Res Commun. 2023;658:1–9.
Article CAS PubMed Google Scholar
Moreira L, Bakir B, Chatterji P, Dantes Z, Reichert M, Rustgi AK. Pancreas 3D organoids: current and future aspects as a research platform for personalized medicine in pancreatic cancer. Cell Mol Gastroenterol Hepatol. 2018;5:289–98.
Article PubMed Google Scholar
Jiang Y, Wang C, Zhou S. Targeting tumor microenvironment in ovarian cancer: premise and promise. Biochim Biophys Acta Rev Cancer. 2020;1873:188361.
Article CAS PubMed Google Scholar
Chaves LP, Melo CM, Saggioro FP, dos Reis RB, Squire JA. Epithelial–mesenchymal transition signaling and prostate cancer stem cells: emerging biomarkers and opportunities for precision therapeutics. Genes (Basel). 2021;12:1900.
Article CAS PubMed Google Scholar
Liu AY, Borges GT, Kanan AD, Pascal LE, Vêncio EF, Vêncio RZN. Prostate cancer reprogramming and dedifferentiation into induced pluripotent stem cells. Cell Sources iPSCs. San Francisco: Elsevier; 2021. p. 163–89.
Yu Y, Jiang W. Pluripotent stem cell differentiation as an emerging model to study human prostate development. Stem Cell Res Ther. 2020;11:1–7.
Lamhamedi-Cherradi S-E, Santoro M, Ramammoorthy V, Menegaz BA, Bartholomeusz G, Iles LR, et al. 3D tissue-engineered model of Ewing’s sarcoma. Adv Drug Deliv Rev. 2014;79:155–71.
Article PubMed Google Scholar
Kuo SZ, Blair KJ, Rahimy E, Kiang A, Abhold E, Fan J-B, et al. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt. BMC Cancer. 2012;12:1–14.
Article CAS Google Scholar
Zhang M, Kumar B, Piao L, Xie X, Schmitt A, Arradaza N, et al. Elevated intrinsic cancer stem cell population in human papillomavirus-associated head and neck squamous cell carcinoma. Cancer. 2014;120:992–1001.
Article PubMed Google Scholar
Djomehri SI, Burman B, Gonzalez ME, Takayama S, Kleer CG. A reproducible scaffold-free 3D organoid model to study neoplastic progression in breast cancer. J Cell Commun Signal. 2019;13:129–43.
Article PubMed Google Scholar
Fang Y, Wang L, Wan C, Sun Y, Van der Jeught K, Zhou Z, et al. MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation. J Clin Invest. 2021;131:e140837.
Article CAS PubMed PubMed Central Google Scholar
Zumwalde NA, Haag JD, Sharma D, Mirrielees JA, Wilke LG, Gould MN, et al. Analysis of immune cells from human mammary ductal epithelial organoids reveals Vδ2+ T cells that efficiently target breast carcinoma cells in the presence of bisphosphonateBisphosphonate activates human breast T cells. Cancer Prev Res. 2016;9:305–16.
Article CAS Google Scholar
Alonso-Nocelo M, Abuín C, López-López R, De La Fuente M. Development and characterization of a three-dimensional co-culture model of tumor T cell infiltration. Biofabrication. 2016;8:25002.
Article CAS Google Scholar
Yuan J, Li X, Yu S. Cancer organoid co-culture model system: novel approach to guide precision medicine. Front Immunol. 2022;13:1061388.
Article CAS PubMed Google Scholar
Miyoshi H, Maekawa H, Kakizaki F, Yamaura T, Kawada K, Sakai Y, et al. An improved method for culturing patient-derived colorectal cancer spheroids. Oncotarget. 2018;9:21950.
Article PubMed PubMed Central Google Scholar
Árnadóttir SS, Jeppesen M, Lamy P, Bramsen JB, Nordentoft I, Knudsen M, et al. Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures. Mol Oncol. 2018;12:132–47.
Article PubMed Google Scholar
Bonnereau J, Courau T, Asesio N, Salfati D, Bouhidel F, Corte H, et al. Autologous T cell responses to primary human colorectal cancer spheroids are enhanced by ectonucleotidase inhibition. Gut. 2023;72:699–709.
Article CAS PubMed Google Scholar
Beaumont KA, Mohana-Kumaran N, Haass NK. Modeling melanoma in vitro and in vivo. Healthcare. 2013;2:27–46.
Article PubMed PubMed Central Google Scholar
Ma HL, Li W, Wang M, Varanda LC, Perussi JR, Zhang YS, et al. In vitro 3D malignant melanoma model for the evaluation of hypericin-loaded oil-in-water microemulsion in photodynamic therapy. Bio-Design Manuf. 2022;5:660–73.
Article CAS Google Scholar
Zamora-Perez P, Xiao C, Sanles-Sobrido M, Rovira-Esteva M, Conesa JJ, Mulens-Arias V, et al. Multiphoton imaging of melanoma 3D models with plasmonic nanocapsules. Acta Biomater. 2022;142:308–19.
Article CAS PubMed Google Scholar
Wang R, Xu J, Juliette L, Castilleja A, Love J, Sung S-Y, et al. Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone. Semin Cancer Biol. 2005;15:353–64.
Article CAS PubMed Google Scholar
Sung S, Chung LWK. Prostate tumor-stroma interaction: Molecular mechanisms and opportunities for therapeutic targeting. Differ Rev. 2002;70:506–21.
Article CAS Google Scholar
Ye M, Zhang H, Yang H, Koche R, Staber PB, Cusan M, et al. Hematopoietic differentiation is required for initiation of acute myeloid leukemia. Cell Stem Cell. 2015;17:611–23.
Article CAS PubMed PubMed Central Google Scholar
Nowak D, Stewart D, Koeffler HP. Differentiation therapy of leukemia: 3 decades of development. Blood, J Am Soc Hematol. 2009;113:3655–65.
CAS Google Scholar
Greaves MF, Chan LC, Furley AJ, Watt SM, Molgaard HV. Lineage promiscuity in hemopoietic differentiation and leukemia. Blood. 1986;67(1):1–11.
Article CAS PubMed Google Scholar
Baker LA, Tiriac H, Clevers H, Tuveson DA. Modeling pancreatic cancer with organoids. Trends Cancer. 2016;2:176–90.
Article PubMed PubMed Central Google Scholar
Chen H, Zhuo Q, Ye Z, Xu X, Ji S. Organoid model: a new hope for pancreatic cancer treatment? Biochim Biophys Acta Rev Cancer. 2021;1875:188466.
Article CAS PubMed Google Scholar
Appleton KM, Elrod AK, Lassahn KA, Shuford S, Holmes LM, DesRochers TM. PD-1/PD-L1 checkpoint inhibitors in combination with olaparib display antitumor activity in ovarian cancer patient-derived three-dimensional spheroid cultures. Cancer Immunol Immunother. 2021;70:843–56.
Article CAS PubMed Google Scholar
Brooks EA, Gencoglu MF, Corbett DC, Stevens KR, Peyton SR. An omentum-inspired 3D PEG hydrogel for identifying ECM-drivers of drug resistant ovarian cancer. APL Bioeng. 2019;3:26106.
Article Google Scholar
Yan F, Gunay G, Valerio TI, Wang C, Wilson JA, Haddad MS, et al. Characterization and quantification of necrotic tissues and morphology in multicellular ovarian cancer tumor spheroids using optical coherence tomography. Biomed Opt Express. 2021;12:3352–71.
Article PubMed PubMed Central Google Scholar
Silvia N, Dai G. Cerebral organoids as a model for glioblastoma multiforme. Curr Opin Biomed Eng. 2020;13:152–9.
Article PubMed PubMed Central Google Scholar
Zhang C, Jin M, Zhao J, Chen J, Jin W. Organoid models of glioblastoma: Advances, applications and challenges. Am J Cancer Res. 2020;10:2242.
CAS PubMed PubMed Central Google Scholar
Linkous A, Balamatsias D, Snuderl M, Edwards L, Miyaguchi K, Milner T, et al. Modeling patient-derived glioblastoma with cerebral organoids. Cell Rep. 2019;26:3203–11.
Article CAS PubMed PubMed Central Google Scholar
Chen G, Yu C, Tang Z, Liu S, An F, Zhu J, et al. Metformin suppresses gastric cancer progression through calmodulin_like protein 3 secreted from tumor_associated fibroblasts. Oncol Rep. 2019;41:405–14.
CAS PubMed Google Scholar
Mu L, Yu W, Su H, Lin Y, Sui W, Yu X, et al. Relationship between the expressions of PD-L1 and tumour-associated fibroblasts in gastric cancer. Artif Cells Nanomed Biotechnol. 2019;47:1036–42.
Article CAS PubMed Google Scholar
Qasrawi A, Arora R, Ramlal R, Munker R, Hildebrandt GC. Allogenic hematopoietic stem cell transplantation for prolonged bone marrow aplasia after chimeric antigen receptor (CAR) T-cell therapy for relapsed diffuse large B-cell lymphoma. Am J Hematol. 2020;95:E89-91.
Article CAS PubMed Google Scholar
Hombach AA, Görgens A, Chmielewski M, Murke F, Kimpel J, Giebel B, et al. Superior therapeutic index in lymphoma therapy: CD30+ CD34+ hematopoietic stem cells resist a chimeric antigen receptor T-cell attack. Mol Ther. 2016;24:1423–34.
Article CAS PubMed PubMed Central Google Scholar
Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol. 2018;15:31–46.
Article CAS PubMed Google Scholar
Chung SS, Koh CJ. Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling. Vitr Cell Dev Biol. 2013;49:746–51.
Article CAS Google Scholar
Xu X-D, Shao S-X, Cao Y-W, Yang X-C, Shi H-Q, Wang Y-L, et al. The study of energy metabolism in bladder cancer cells in co-culture conditions using a microfluidic chip. Int J Clin Exp Med. 2015;8:12327.
CAS PubMed PubMed Central Google Scholar
Huang L, Holtzinger A, Jagan I, BeGora M, Lohse I, Ngai N, et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell–and patient-derived tumor organoids. Nat Med. 2015;21:1364–71.
Article CAS PubMed PubMed Central Google Scholar
Beutel AK, Schütte L, Scheible J, Roger E, Müller M, Perkhofer L, et al. A prospective feasibility trial to challenge patient–derived pancreatic cancer organoids in predicting treatment response. Cancers (Basel). 2021;13:2539.
Article CAS PubMed Google Scholar
Dantes Z, Yen H-Y, Pfarr N, Winter C, Steiger K, Muckenhuber A, et al. Implementing cell-free DNA of pancreatic cancer patient–derived organoids for personalized oncology. JCI Insight. 2020;5:e137809.
Article PubMed PubMed Central Google Scholar
Nagle PW, Plukker JTM, Muijs CT, van Luijk P, Coppes RP. Patient-derived tumor organoids for prediction of cancer treatment response. Semin Cancer Biol. 2018;53:258–64.
Article CAS PubMed Google Scholar
Demyan L, Habowski AN, Plenker D, King DA, Standring OJ, Tsang C, et al. Pancreatic cancer patient-derived organoids can predict response to neoadjuvant chemotherapy. Ann Surg. 2022;276:450–62.
Article PubMed Google Scholar
Gao S, Shen J, Hornicek F, Duan Z. Three-dimensional (3D) culture in sarcoma research and the clinical significance. Biofabrication. 2017;9:32003.
Article Google Scholar
Bassi G, Panseri S, Dozio SM, Sandri M, Campodoni E, Dapporto M, et al. Scaffold-based 3D cellular models mimicking the heterogeneity of osteosarcoma stem cell niche. Sci Rep. 2020;10:1–12.
Article Google Scholar
Skardal A, Devarasetty M, Rodman C, Atala A, Soker S. Liver-tumor hybrid organoids for modeling tumor growth and drug response in vitro. Ann Biomed Eng. 2015;43:2361–73.
Article PubMed PubMed Central Google Scholar
Nuciforo S, Fofana I, Matter MS, Blumer T, Calabrese D, Boldanova T, et al. Organoid models of human liver cancers derived from tumor needle biopsies. Cell Rep. 2018;24:1363–76.
Article CAS PubMed PubMed Central Google Scholar
Cao W, Liu J, Wang L, Li M, Verstegen MMA, Yin Y, et al. Modeling liver cancer and therapy responsiveness using organoids derived from primary mouse liver tumors. Carcinogenesis. 2019;40:145–54.
Article CAS PubMed Google Scholar
Nuciforo S, Heim MH. Organoids to model liver disease. JHEP Reports. 2021;3: 100198.
Article PubMed Google Scholar
Zhu X, Zhang B, He Y, Bao J. Liver organoids: Formation strategies and biomedical applications. Tissue Eng Regen Med. 2021;18:573–85.
Article PubMed PubMed Central Google Scholar
Young M, Rodenhizer D, Dean T, D’Arcangelo E, Xu B, Ailles L, et al. A TRACER 3D Co-Culture tumour model for head and neck cancer. Biomaterials. 2018;164:54–69.
Article CAS PubMed Google Scholar
West GW, Weichselbaum R, Little JB. Limited penetration of methotrexate into human osteosarcoma spheroids as a proposed model for solid tumor resistance to adjuvant chemotherapy. Cancer Res. 1980;40:3665–8.
CAS PubMed Google Scholar
León IE, Cadavid-Vargas JF, Resasco A, Maschi F, Ayala MA, Carbone C, et al. In vitro and in vivo antitumor effects of the VO-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice. JBIC J Biol Inorg Chem. 2016;21:1009–20.
Article PubMed Google Scholar
Chow T, Wutami I, Lucarelli E, Choong PF, Duchi S, Di Bella C. Creating in vitro three-dimensional tumor models: a guide for the biofabrication of a primary osteosarcoma model. Tissue Eng Part B Rev. 2021;27:514–29.
Article PubMed Google Scholar
Sachdeva UM, Shimonosono M, Flashner S, Cruz-Acuña R, Gabre JT, Nakagawa H. Understanding the cellular origin and progression of esophageal cancer using esophageal organoids. Cancer Lett. 2021;509:39–52.
Article CAS PubMed PubMed Central Google Scholar
Whelan KA, Muir AB, Nakagawa H. Esophageal 3D culture systems as modeling tools in esophageal epithelial pathobiology and personalized medicine. Cell Mol Gastroenterol Hepatol. 2018;5:461–78.
Article PubMed PubMed Central Google Scholar
Risbridger GP, Toivanen R, Taylor RA. Preclinical models of prostate cancer: patient-derived xenografts, organoids, and other explant models. Cold Spring Harb Perspect Med. 2018;8: a030536.
Article PubMed PubMed Central Google Scholar
Drost J, Karthaus WR, Gao D, Driehuis E, Sawyers CL, Chen Y, et al. Organoid culture systems for prostate epithelial and cancer tissue. Nat Protoc. 2016;11:347–58.
Article CAS PubMed PubMed Central Google Scholar
Puca L, Bareja R, Prandi D, Shaw R, Benelli M, Karthaus WR, et al. Patient derived organoids to model rare prostate cancer phenotypes. Nat Commun. 2018;9:2404.
Article PubMed PubMed Central Google Scholar
Eder T, Eder IE. 3D hanging drop culture to establish prostate cancer organoids. 3d Cell Cult Methods Protoc. 2017;167–75.
Gilbert CA, Ross AH. Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem. 2009;108:1031–8.
Article CAS PubMed PubMed Central Google Scholar
Ou J, Guan D, Yang Y. Non-contact co-culture with human vascular endothelial cells promotes epithelial-to-mesenchymal transition of cervical cancer SiHa cells by activating the NOTCH1/LOX/SNAIL pathway. Cell Mol Biol Lett. 2019;24:1–11.
Article CAS Google Scholar
Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant. 2005;35:835–57.
Article CAS PubMed Google Scholar
Luevano M, Madrigal A, Saudemont A. Generation of natural killer cells from hematopoietic stem cells in vitro for immunotherapy. Cell Mol Immunol. 2012;9:310–20.
Article CAS PubMed PubMed Central Google Scholar
Wu G, Wu J, Li Z, Shi S, Wu D, Wang X, et al. Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy. Bio-Design Manuf. 2022;5:437–50.
Article CAS Google Scholar
Dong R, Zhang B, Zhang X. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci. 2022;12:1–16.
Article Google Scholar
Devarasetty M, Mazzocchi AR, Skardal A. Applications of bioengineered 3D tissue and tumor organoids in drug development and precision medicine: current and future. BioDrugs. 2018;32:53–68.
Article CAS PubMed PubMed Central Google Scholar
Grimm D, Bauer J, Hofstädter F, Riegger GAJ, Kromer EP. Characteristics of multicellular spheroids formed by primary cultures of human thyroid tumor cells. Thyroid. 1997;7:859–65.
Article CAS PubMed Google Scholar
Cirello V, Vaira V, Grassi ES, Vezzoli V, Ricca D, Colombo C, et al. Multicellular spheroids from normal and neoplastic thyroid tissues as a suitable model to test the effects of multikinase inhibitors. Oncotarget. 2017;8:9752.
Article PubMed Google Scholar
Pietsch J, Ma X, Wehland M, Aleshcheva G, Schwarzwälder A, Segerer J, et al. Spheroid formation of human thyroid cancer cells in an automated culturing system during the Shenzhou-8 Space mission. Biomaterials. 2013;34:7694–705.
Article CAS PubMed Google Scholar
Diem MC. Engineered stem cells power expansive range of cancer therapies. Biopharma Deal. 2021;4985.
Baudino TA. Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol. 2015;12:3–20.
Article CAS PubMed Google Scholar
Nishikawa S, Goldstein RA, Nierras CR. The promise of human induced pluripotent stem cells for research and therapy. Nat Rev Mol cell Biol. 2008;9:725–9.
Article CAS PubMed Google Scholar
Sayed N, Ameen M, Wu JC. Personalized medicine in cardio-oncology: The role of induced pluripotent stem cell. Cardiovasc Res. 2019;115:949–59.
Article CAS PubMed PubMed Central Google Scholar
Ware CB, Nelson AM, Mecham B, Hesson J, Zhou W, Jonlin EC, et al. Derivation of naïve human embryonic stem cells. Proc Natl Acad Sci U S A. 2014;111:4484–9.
Article CAS PubMed PubMed Central Google Scholar
Ouyang X, Telli ML, Wu JC. Induced pluripotent stem cell-based cancer vaccines. Front Immunol. 2019;10:1510.
Article CAS PubMed PubMed Central Google Scholar
Seton-Rogers S. Immunotherapy: iPSC-based vaccines provoke a response. Nat Rev Cancer. 2018;18:207.
Article CAS PubMed Google Scholar
Choi KD, Vodyanik MA, Slukvin II. Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell-derived lin-CD34+CD43 +CD45+ progenitors. J Clin Invest. 2009;119:2818–29.
Article CAS PubMed PubMed Central Google Scholar
Jiang Z, Han Y, Cao X. Induced pluripotent stem cell (iPSCs) and their application in immunotherapy. Cell Mol Immunol. 2014;11:17–24.
Article CAS PubMed Google Scholar
Gąbka-Buszek A, Kwiatkowska-Borowczyk E, Jankowski J, Kozłowska AK, Mackiewicz A. Novel genetic melanoma vaccines based on induced pluripotent stem cells or melanosphere-derived stem-like cells display high efficacy in a murine tumor rejection model. Vaccines. 2020;8:147.
Article PubMed PubMed Central Google Scholar
Yuan X, Clarke R, Lai Y-S, Chang C-W, Yang B-H, Hsia G, et al. Clinical manufacture of FT819: use of a clonal multiplexed-engineered master induced pluripotent stem cell line to mass produce off-the-shelf CAR T-cell therapy. Blood. 2021;138:1766–1766.
Article Google Scholar
Itoh M, Kawagoe S, Nakagawa H, Asahina A, Okano HJ. Generation of induced pluripotent stem cell (iPSC) from NY-ESO-I-specific cytotoxic T cells isolated from the melanoma patient with minor HLAs: the practical pilot study for the adoptive immunotherapy for melanoma using iPSC technology. Exp Dermatol. 2023;32:126–34.
Article CAS PubMed Google Scholar
Chiu E, Felices M, Cichocki F, Davis Z, Wang H, Tuninga K, et al. Anti-NKG2C/IL-15/anti-CD33 killer engager directs primary and iPSC-derived NKG2C+ NK cells to target myeloid leukemia. Mol Ther. 2021;29:3410–21.
Article CAS PubMed PubMed Central Google Scholar
Loh JK, Wang ML, Cheong SK, Tsai FT, Huang SH, Wu JR, et al. The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells. J Chinese Med Assoc. 2022;85:821–30.
Article CAS Google Scholar
Li Z, Yang L. Current status of producing autologous hematopoietic stem cells. Curr Res Transl Med. 2023;71:103377.
CAS PubMed Google Scholar
Sadeqi Nezhad M, Abdollahpour-Alitappeh M, Rezaei B, Yazdanifar M, Seifalian AM. Induced pluripotent stem cells (iPSCs) provide a potentially unlimited T cell source for CAR-T cell development and off-the-shelf products. Pharm Res. 2021;38:931–45.
Article CAS PubMed Google Scholar
Musunuru K, Sheikh F, Gupta RM, Houser SR, Maher KO, Milan DJ, et al. Induced pluripotent stem cells for cardiovascular disease modeling and precision medicine: a scientific statement from the American Heart Association. Circ Genomic Precis Med. 2018;11: e000043.
Google Scholar
Saha K, Jaenisch R. Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell. 2009;5:584–95.
Article CAS PubMed PubMed Central Google Scholar
Tapia N, Schöler HR. Molecular obstacles to clinical translation of iPSCs. Cell Stem Cell. 2016;19:298–309.
Article CAS PubMed Google Scholar
Wang L, Chen Y, Guan C, Zhao Z, Li Q, Yang J, et al. Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells. Stem Cell Res Ther. 2017;8:1–13.
Article Google Scholar
Kang X, Yu Q, Huang Y, Song B, Chen Y, Gao X, et al. Effects of integrating and non-integrating reprogramming methods on copy number variation and genomic stability of human induced pluripotent stem cells. PLoS ONE. 2015;10: e0131128.
Article PubMed PubMed Central Google Scholar
Andrews PW, Ben-David U, Benvenisty N, Coffey P, Eggan K, Knowles BB, et al. Assessing the safety of human pluripotent stem cells and their derivatives for clinical applications. Stem cell reports. 2017;9:1–4.
Article PubMed PubMed Central Google Scholar
Carpenter MK, Frey-Vasconcells J, Rao MS. Developing safe therapies from human pluripotent stem cells. Nat Biotechnol. 2009;27:606–13.
Article CAS PubMed Google Scholar
Ishii T, Pera RAR, Greely HT. Ethical and legal issues arising in research on inducing human germ cells from pluripotent stem cells. Cell Stem Cell. 2013;13:145–8.
Article CAS PubMed Google Scholar
Moradi S, Mahdizadeh H, Šarić T, Kim J, Harati J, Shahsavarani H, et al. Research and therapy with induced pluripotent stem cells (iPSCs): Social, legal, and ethical considerations. Stem Cell Res Ther. 2019;10:1–13.
Article Google Scholar
Orzechowski M, Schochow M, Kühl M, Steger F. Content and method of information for participants in clinical studies with induced pluripotent stem cells (iPSCs). Front Cell Dev Biol. 2021;9: 627816.
Article PubMed PubMed Central Google Scholar
Yaffe MP, Noggle SA, Solomon SL. Raising the standards of stem cell line quality. Nat Cell Biol. 2016;18:236–7.
Article PubMed Google Scholar
Ray A, Joshi JM, Sundaravadivelu PK, Raina K, Lenka N, Kaveeshwar V, et al. An overview on promising somatic cell sources utilized for the efficient generation of induced pluripotent stem cells. Stem Cell Rev Reports. 2021;17:1954–74.
Article Google Scholar
Lo Sardo V, Ferguson W, Erikson GA, Topol EJ, Baldwin KK, Torkamani A. Influence of donor age on induced pluripotent stem cells. Nat Biotechnol. 2017;35:69–74.
Article CAS PubMed Google Scholar
Wang AYL. Application of modified mrna in somatic reprogramming to pluripotency and directed conversion of cell fate. Int J Mol Sci. 2021;22:8148.
Article CAS PubMed PubMed Central Google Scholar
Lin T, Wu S. Reprogramming with small molecules instead of exogenous transcription factors. Stem Cells Int. 2015;2015:794632.
Article PubMed PubMed Central Google Scholar
Smith C, Gore A, Yan W, Abalde-Atristain L, Li Z, He C, et al. Whole-genome sequencing analysis reveals high specificity of CRISPR/Cas9 and TALEN-based genome editing in human iPSCs. Cell Stem Cell. 2014;15:12–3.
Article CAS PubMed PubMed Central Google Scholar
Neofytou E, O’Brien CG, Couture LA, Wu JC. Hurdles to clinical translation of human induced pluripotent stem cells. J Clin Invest. 2015;125:2551–7.
Article PubMed PubMed Central Google Scholar
Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med. 2013;19:998–1004.
Article CAS PubMed PubMed Central Google Scholar
Doss MX, Sachinidis A. Current challenges of iPSC-based disease modeling and therapeutic implications. Cells. 2019;8:403.
Article CAS PubMed PubMed Central Google Scholar
Harding J, Mirochnitchenko O. Preclinical studies for induced pluripotent stem cell-based therapeutics. J Biol Chem. 2014;289:4585–93.
Article CAS PubMed Google Scholar
O’Shea O, Steeg R, Chapman C, Mackintosh P, Stacey GN. Development and implementation of large-scale quality control for the European bank for induced pluripotent stem cells. Stem Cell Res. 2020;45: 101773.
Article PubMed Google Scholar
Rohani L, Johnson AA, Naghsh P, Rancourt DE, Ulrich H, Holland H. Concise review: molecular cytogenetics and quality control: clinical guardians for pluripotent stem cells. Stem Cells Transl Med. 2018;7:867–75.
Article PubMed PubMed Central Google Scholar
Baghbaderani BA, Tian X, Neo BH, Burkall A, Dimezzo T, Sierra G, et al. cGMP-manufactured human induced pluripotent stem cells are available for pre-clinical and clinical applications. Stem cell reports. 2015;5:647–59.
Article CAS PubMed PubMed Central Google Scholar
Olsson H. Cell of origin of breast cancer: an updated hypothesis merging epidemiological data with molecular biology. J Carcinog Mutagen. 2013;4:139.
Article Google Scholar
Taurin S, Alkhalifa H. Breast cancers, mammary stem cells, and cancer stem cells, characteristics, and hypotheses. Neoplasia. 2020;22:663–78.
Article CAS PubMed PubMed Central Google Scholar
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.
Article CAS PubMed PubMed Central Google Scholar
Michishita M. Understanding of tumourigenesis in canine mammary tumours based on cancer stem cell research. Vet J. 2020;265:105560.
Article CAS PubMed Google Scholar
Sims AH, Howell A, Howell SJ, Clarke RB. Origins of breast cancer subtypes and therapeutic implications. Nat Clin Pract Oncol. 2007;4:516–25.
Article CAS PubMed Google Scholar
Osmond B, Facey COB, Zhang C, Boman BM. HOXA9 overexpression contributes to stem cell overpopulation that drives development and growth of colorectal cancer. Int J Mol Sci. 2022;23:6799.
Article CAS PubMed PubMed Central Google Scholar
Tang J, Fewings E, Chang D, Zeng H, Liu S, Jorapur A, et al. The genomic landscapes of individual melanocytes from human skin. Nature. 2020;586:600–5.
Article CAS PubMed PubMed Central Google Scholar
Darp R, Ceol C. Making a melanoma: Molecular and cellular changes underlying melanoma initiation. Pigment Cell Melanoma Res. 2021;34:280–7.
Article CAS PubMed Google Scholar
Parikh KR, Dhotre SV, Satasiya AH. A retrospective histopathological study of non-melanocytic skin tumors. Ann Pathol Lab Med. 2022;9:A27-34.
Article Google Scholar
Sala M, Ros M, Saltel F. A complex and evolutive character: two face aspects of ECM in tumor progression. Front Oncol. 2020;10:1620.
Article PubMed PubMed Central Google Scholar
Rahmani F, Safavi P, Fathollahpour A, Sabz FT, Tajzadeh P, Arefnezhad M, et al. The interplay between non-coding RNAs and Wnt/ß-catenin signaling pathway in urinary tract cancers: from tumorigenesis to metastasis. EXCLI J. 2022;21:1273.
Rahmani F, Zandigohar M, Safavi P, Behzadi M, Ghorbani Z, Payazdan M, et al. The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis. Current Pharmaceutical Design. 2023;29(10):766–76.
Article CAS PubMed Google Scholar
Bassel A, Abdulkareem AB, Alyasseri ZAA, Sani NS, Mohammed HJ. Automatic malignant and benign skin cancer classification using a hybrid deep learning approach. Diagnostics. 2022;12:2472.
Article PubMed PubMed Central Google Scholar
Woo YR, Cho SH, Lee JD, Kim HS. The Human Microbiota and Skin Cancer. Int J Mol Sci. 2022;23:1813.
Article CAS PubMed PubMed Central Google Scholar
He J, Xiong L, Li Q, Lin L, Miao X, Yan S, et al. 3D modeling of cancer stem cell niche. Oncotarget. 2018;9:1326–45.
Article PubMed Google Scholar
Saha K, Mei Y, Reisterer CM, Pyzocha NK, Yang J, Muffat J, et al. Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions. Proc Natl Acad Sci U S A. 2011;108:18714–9.
Article CAS PubMed PubMed Central Google Scholar
CSCs and pluripotent/multipotent stem cells. Mod. Pathol. 2017:1336–7.
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461–73.
Article CAS PubMed Google Scholar
Zhang M, Vandana JJ, Lacko L, Chen S. Modeling cancer progression using human pluripotent stem cell-derived cells and organoids. Stem Cell Res. 2020;49:102063.
Article CAS PubMed PubMed Central Google Scholar
Xie N, Shen G, Gao W, Huang Z, Huang C, Fu L. Neoantigens: promising targets for cancer therapy. Signal Transduct Target Ther. 2023;8:9.
Article CAS PubMed PubMed Central Google Scholar
Lefort S, El-Naggar A, Tan S, Colborne S, Negri GL, Pellacani D, et al. De novo and cell line models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer. Cell Death Differ. 2022;29:54–64.
Article CAS PubMed Google Scholar
Sancho-Martinez I, Nivet E, Xia Y, Hishida T, Aguirre A, Ocampo A, et al. Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. Nat Commun. 2016;7:10743.
Article CAS PubMed PubMed Central Google Scholar
Yucer N, Holzapfel M, Jenkins Vogel T, Lenaeus L, Ornelas L, Laury A, et al. Directed differentiation of human induced pluripotent stem cells into Fallopian Tube Epithelium. Sci Rep. 2017;7:10741.
Article PubMed PubMed Central Google Scholar
Montserrat N, Ramírez-Bajo MJ, Xia Y, Sancho-Martinez I, Moya-Rull D, Miquel-Serra L, et al. Generation of induced pluripotent stem cells from human renal proximal tubular cells with only two transcription factors, OCT4 and SOX2. J Biol Chem. 2012;287:24131–8.
Article CAS PubMed PubMed Central Google Scholar
Vizcardo R, Masuda K, Yamada D, Ikawa T, Shimizu K, Fujii S-I, et al. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell. 2013;12:31–6.
Article CAS PubMed Google Scholar
Lu S, Zhang Z, Du P, Chard LS, Yan W, El KM, et al. A virus-infected, reprogrammed somatic cell–derived tumor cell (VIREST) vaccination regime can prevent initiation and progression of pancreatic cancer. Clin Cancer Res. 2020;26:465–76.
Article CAS PubMed Google Scholar
Sancho-Martinez I, Nivet E, Xia Y, Hishida T, Aguirre A, Ocampo A, et al. Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. Nat Commun. 2016;7:10743.
Article CAS PubMed PubMed Central Google Scholar
Koga T, Chaim IA, Benitez JA, Markmiller S, Parisian AD, Hevner RF, et al. Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells. Nat Commun. 2020;11:550.
Article CAS PubMed PubMed Central Google Scholar
Ingber DE. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet. 2022;23:467–91.
Article CAS PubMed PubMed Central Google Scholar
Steinberg GM. The militarization of space. From passive support to active weapons systems. Futures. 1982;14:374–92.
Article Google Scholar
Thornton CD, Fielding S, Karbowniczek K, Roig-Merino A, Burrows AE, FitzPatrick LM, et al. Safe and stable generation of induced pluripotent stem cells using doggybone DNA vectors. Mol Ther Methods Clin Dev. 2021;23:348–58.
Article CAS PubMed PubMed Central Google Scholar
Shamsian A, Sahebnasagh R, Norouzy A, Hussein SH, Ghahremani MH, Azizi Z. Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther. 2022;13:459.
Article PubMed PubMed Central Google Scholar
Pan X-Y, Tsai M-H, Wuputra K, Ku C-C, Lin W-H, Lin Y-C, et al. Application of cancer cell reprogramming technology to human cancer research. Anticancer Res. 2017;37:3367–77.
Article CAS PubMed Google Scholar
Katt ME, Placone AL, Wong AD, Xu ZS, Searson PC. In vitro tumor models: advantages, disadvantages, variables, and selecting the right platform. Front Bioeng Biotechnol. 2016;4:12.
Article PubMed PubMed Central Google Scholar
Goodspeed A, Heiser LM, Gray JW, Costello JC. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol Cancer Res. 2016;14:3–13.
Article CAS PubMed Google Scholar
Zhao MT, Chen H, Liu Q, Shao NY, Sayed N, Wo HT, et al. Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs. Proc Natl Acad Sci U S A. 2017;114:E11111–20.
Article CAS PubMed PubMed Central Google Scholar
Sharma A, Sances S, Workman MJ, Svendsen CN. Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery. Cell Stem Cell. 2020;26:309–29.
Article CAS PubMed PubMed Central Google Scholar
Prakash P, Widjaja J, Marcella C, Sun B. Evaluation of the sensitivity and specificity of circulating microRNAs to diagnose breast cancer: A systematic review and meta-analysis. Int J Sci Res Dent Med Sci. 2023;5(1):35–47.
CAS Google Scholar
Chao MP, Gentles AJ, Chatterjee S, Lan F, Reinisch A, Corces MR, et al. Human AML-iPSCs reacquire leukemic properties after differentiation and model clonal variation of disease. Cell Stem Cell. 2017;20:329-344.e7.
Article CAS PubMed PubMed Central Google Scholar
Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F, Gonen M, et al. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat Biotechnol. 2013;31:928–33.
Article CAS PubMed PubMed Central Google Scholar
Poetsch MS, Strano A, Guan K. Human induced pluripotent stem cells: from cell origin, genomic stability, and epigenetic memory to translational medicine. Stem Cells. 2022;40:546–55.
Article PubMed PubMed Central Google Scholar
Xu X, Zhong Z. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells. Acta Pharmacol Sin. 2013;34:755–64.
Article CAS PubMed PubMed Central Google Scholar
Kim J, Hoffman JP, Alpaugh RK, Rhim AD, Reichert M, Stanger BZ, et al. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep. 2013;3:2088–99.
Article CAS PubMed PubMed Central Google Scholar
Sidhu I, Barwe SP, Pillai RK, Gopalakrishnapillai A. Harnessing the power of induced pluripotent stem cells and gene editing technology: therapeutic implications in hematological malignancies. Cells. 2021;10:2698.
Article CAS PubMed PubMed Central Google Scholar
Crespo M, Vilar E, Tsai SY, Chang K, Amin S, Srinivasan T, et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med. 2017;23:878–84.
Article CAS PubMed PubMed Central Google Scholar
Lovell-Badge R, Anthony E, Barker RA, Bubela T, Brivanlou AH, Carpenter M, et al. ISSCR guidelines for stem cell res clinical translation: The 2021 update. Stem Cell Rep. 2021;16:1398–408.
Article Google Scholar
Engle SJ, Puppala D. Integrating human pluripotent stem cells into drug development. Cell Stem Cell. 2013;12:669–77.
Article CAS PubMed Google Scholar
Gingold J, Zhou R, Lemischka IR, Lee D-F. Modeling cancer with pluripotent stem cells. Trends in cancer. 2016;2:485–94.
Article PubMed PubMed Central Google Scholar
Chakravarthi BVSK, Nepal S, Varambally S. Genomic and epigenomic alterations in cancer. Am J Pathol. 2016;186:1724–35.
Article CAS PubMed PubMed Central Google Scholar
Kominsky SL. Claudins: emerging targets for cancer therapy. Expert Rev Mol Med. 2006;8:1–11.
Article PubMed Google Scholar
Fedele C, Tothill RW, McArthur GA. Navigating the challenge of tumor heterogeneity in cancer therapy. Cancer Discov. 2014;4:146–8.
Article CAS PubMed Google Scholar
Xu H, Lyu X, Yi M, Zhao W, Song Y, Wu K. Organoid technology and applications in cancer research. J Hematol Oncol. 2018;11:1–15.
Article PubMed PubMed Central Google Scholar
Xia T, Du W, Chen X, Zhang Y. Organoid models of the tumor microenvironment and their applications. J Cell Mol Med. 2021;25:5829–41.
Article PubMed PubMed Central Google Scholar
Lai Y, Wei X, Lin S, Qin L, Cheng L, Li P. Current status and perspectives of patient-derived xenograft models in cancer research. J Hematol Oncol. 2017;10:1–14.
Article Google Scholar
Min H-Y, Lee H-Y. Molecular targeted therapy for anticancer treatment. Exp Mol Med. 2022;54:1670–94.
Article CAS PubMed PubMed Central Google Scholar
Li Y, Li L, Chen Z-N, Gao G, Yao R, Sun W. Engineering-derived approaches for iPSC preparation, expansion, differentiation and applications. Biofabrication. 2017;9:32001.
Article Google Scholar
Nicholson MW, Ting C-Y, Chan DZH, Cheng Y-C, Lee Y-C, Hsu C-C, et al. Utility of iPSC-derived cells for disease modeling, drug development, and cell therapy. Cells. 2022;11:1853.
Article CAS PubMed PubMed Central Google Scholar
Ebert AD, Svendsen CN. Human stem cells and drug screening: opportunities and challenges. Nat Rev Drug Discov. 2010;9:367–72.
Article CAS PubMed Google Scholar
Qiao Y, Agboola OS, Hu X, Wu Y, Lei L. Tumorigenic and immunogenic properties of induced pluripotent stem cells: a promising cancer vaccine. Stem cell Rev reports. 2020;16:1049–61.
Article Google Scholar
Zhang M, Vandana JJ, Lacko L, Chen S. Modeling cancer progression using human pluripotent stem cell-derived cells and organoids. Stem Cell Res. 2020;49: 102063.
Article CAS PubMed PubMed Central Google Scholar
Zheng YL. Some ethical concerns about human induced pluripotent stem cells. Sci Eng Ethics. 2016;22:1277–84.
Article PubMed Google Scholar
Cheung P, Xiol J, Dill MT, Yuan W-C, Panero R, Roper J, et al. Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer. Cell Stem Cell. 2020;27:590-604.e9.
Article CAS PubMed PubMed Central Google Scholar
Kim S-Y, Lee JY, Kim DH, Joo H-S, Yun MR, Jung D, et al. Patient-derived cells to guide targeted therapy for advanced lung adenocarcinoma. Sci Rep. 2019;9:19909.
Article CAS PubMed PubMed Central Google Scholar
Hao M, Cao Z, Wang Z, Xin J, Kong B, Xu J, et al. Patient-derived organoid model in the prediction of chemotherapeutic drug response in colorectal cancer. ACS Biomater Sci Eng. 2022;8:3515–25.
Article CAS PubMed Google Scholar
Haque MR, Wessel CR, Leary DD, Wang C, Bhushan A, Bishehsari F. Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment. Microsyst Nanoeng. 2022;8:36.
Article PubMed PubMed Central Google Scholar
Lõhmussaar K, Oka R, Espejo Valle-Inclan J, Smits MHH, Wardak H, Korving J, et al. Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer. Cell Stem Cell. 2021;28:1380-1396.e6.
Article PubMed Google Scholar
Starling S. Stem cell hope for cancer treatment. Nat Rev Immunol. 2018;18:223.
Article CAS PubMed Google Scholar
Hepburn AC, Steele RE, Veeratterapillay R, Wilson L, Kounatidou EE, Barnard A, et al. The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance. Oncogene. 2019;38:4412–24.
Article CAS PubMed PubMed Central Google Scholar
Du J, Xu Y, Sasada S, Oo AKK, Hassan G, Mahmud H, et al. Signaling inhibitors accelerate the conversion of mouse iPS Cells into cancer stem cells in the tumor microenvironment. Sci Rep. 2020;10:9955.
Article CAS PubMed PubMed Central Google Scholar
Zhou Y, Li M, Zhou K, Brown J, Tsao T, Cen X, et al. Engineering induced pluripotent stem cells for cancer immunotherapy. Cancers (Basel). 2022;14:2266.
Article CAS PubMed Google Scholar
Bloor AJC, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, et al. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nat Med. 2020;26:1720–5.
Article CAS PubMed Google Scholar
Cichocki F, Bjordahl R, Gaidarova S, Mahmood S, Rogers P, Ge MQ, et al. iPSC-derived NK cells and Anti-PD-1 antibody synergize to enhance T cell cytokine and cytolytic responses against multiple tumors. Blood. 2018;132:730.
Article Google Scholar
Vandana JJ, Manrique C, Lacko LA, Chen S. Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation. Cell Stem Cell. 2023;30:571–91.
Article CAS PubMed Google Scholar
Huang CY, Nicholson MW, Wang JY, Ting CY, Tsai MH, Cheng YC, et al. Population-based high-throughput toxicity screen of human iPSC-derived cardiomyocytes and neurons. Cell Rep. 2022;39: 110643.
Article CAS PubMed Google Scholar
Elitt MS, Barbar L, Tesar PJ. Drug screening for human genetic diseases using iPSC models. Hum Mol Genet. 2018;27:R89-98.
Article CAS PubMed PubMed Central Google Scholar
Woan KV, Kim H, Bjordahl R, Davis ZB, Gaidarova S, Goulding J, et al. Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy. Cell Stem Cell. 2021;28:2062-2075.e5.
Article CAS PubMed Google Scholar
Kaneko S. Successful organoid-mediated generation of iPSC-derived CAR-T cells. Cell Stem Cell. 2022;29:493–5.
Article CAS PubMed Google Scholar
de Jesus BB, Neves BM, Ferreira M, Nóbrega-Pereira S. Strategies for cancer immunotherapy using induced pluripotency stem cells-based vaccines. Cancers (Basel). 2020;12:3581.
Article Google Scholar
Takaaki O, Kenichi M, Ryutaro K, Toshihiro Y, Ryoko A, Masumi A, et al. In situ delivery of iPSC-derived dendritic cells with local radiotherapy generates systemic antitumor immunity and potentiates PD-L1 blockade in preclinical poorly immunogenic tumor models. J Immunother Cancer. 2021;9: e002432.
Article Google Scholar
Laskowski TJ, Biederstädt A, Rezvani K. Natural killer cells in antitumour adoptive cell immunotherapy. Nat Rev Cancer. 2022;22:557–75.
Article CAS PubMed PubMed Central Google Scholar
Vinel C, Rosser G, Guglielmi L, Constantinou M, Pomella N, Zhang X, et al. Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma. Nat Commun. 2021;12:6130.
Article CAS PubMed PubMed Central Google Scholar
Chen Y-W, Huang SX, de Carvalho ALRT, Ho S-H, Islam MN, Volpi S, et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol. 2017;19:542–9.
Article CAS PubMed PubMed Central Google Scholar
Ito E, Miyagawa S, Takeda M, Kawamura A, Harada A, Iseoka H, et al. Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application. Sci Rep. 2019;9:1881.
Article PubMed PubMed Central Google Scholar
Yasuda S, Kusakawa S, Kuroda T, Miura T, Tano K, Takada N, et al. Tumorigenicity-associated characteristics of human iPS cell lines. PLoS ONE. 2018;13: e0205022.
Article PubMed PubMed Central Google Scholar
Zhang C, Hu Y, Xiao W, Tian Z. Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy. Cell Mol Immunol. 2021;18:2083–100.
Article CAS PubMed PubMed Central Google Scholar
Wang Z, Chen H, Wang P, Zhou M, Li G, Hu Z, et al. Site-specific integration of TRAIL in iPSC-derived mesenchymal stem cells for targeted cancer therapy. Stem Cells Transl Med. 2022;11:297–309.
Article CAS PubMed PubMed Central Google Scholar
Park JH, Jain N, Chen A, McGuirk JP, Diaz M, Valamehr B, et al. A phase I study of FT819, a first-of-kind, off-the-shelf, iPSC-derived TCR-less CD19 CAR T cell therapy for the treatment of relapsed/refractory B-cell malignancies. Blood. 2020;136:15–6.
Article Google Scholar
Goldenson BH, Hor P, Kaufman DS. iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting. Front Immunol. 2022;13:841107.
Article CAS PubMed PubMed Central Google Scholar
Zhang Z, Lu S, Dunmall LSC, Wang Z, Cheng Z, Zhang Z, et al. Treatment and prevention of lung cancer using a virus-infected reprogrammed somatic cell-derived tumor cell vaccination (VIReST) regime. Front Immunol. 2020;11:1996.
Article CAS PubMed PubMed Central Google Scholar
Nguyen R, Da Won BS, Qiao L, George J. Developing liver organoids from induced pluripotent stem cells (iPSCs): an alternative source of organoid generation for liver cancer research. Cancer Lett. 2021;508:13–7.
Article CAS PubMed Google Scholar
Vizcardo R, Klemen ND, Islam R, Gurusamy D, Tamaoki N, Jia L, et al. Developing the next generation of iPSC cell-based immunotherapies. Blood. 2018;132:3707–3707.
Article Google Scholar
Wu Q, Liu J, Wang X, Feng L, Wu J, Zhu X, et al. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online. 2020;19:9.
Article PubMed PubMed Central Google Scholar
Parfejevs V, Sagini K, Buss A, Sobolevska K, Llorente A, Riekstina U, et al. Adult stem cell-derived extracellular vesicles in cancer treatment: opportunities and challenges. Cells. 2020;9:1171.
Article CAS PubMed PubMed Central Google Scholar
Zhang L, Tian L, Dai X, Yu H, Wang J, Lei A, et al. Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions. J Hematol Oncol. 2020;13:153.
Article CAS PubMed PubMed Central Google Scholar
Becklin KL, Draper GM, Madden RA, Kluesner MG, Koga T, Huang M, et al. Developing bottom-up induced pluripotent stem cell derived solid tumor models using precision genome editing technologies. Cris J. 2022;5:517–35.
Article CAS Google Scholar
Mashima H, Zhang R, Kobayashi T, Tsukamoto H, Liu T, Iwama T, et al. Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy. Mol Ther Methods Clin Dev. 2021;21:171–9.
Article CAS PubMed PubMed Central Google Scholar
Cao Y, Wang X, Jin T, Tian Y, Dai C, Widarma C, et al. Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy. Signal Transduct Target Ther. 2020;5:250.
Article PubMed PubMed Central Google Scholar
Zhang R, Zhang L, Xie X. iPSCs and small molecules: a reciprocal effort towards better approaches for drug discovery. Acta Pharmacol Sin. 2013;34:765–76.
Article CAS PubMed PubMed Central Google Scholar
Palechor-Ceron N, Krawczyk E, Dakic A, Simic V, Yuan H, Blancato J, et al. Conditional reprogramming for patient-derived cancer models and next-generation living biobanks. Cells. 2019;8:1327.
Article CAS PubMed PubMed Central Google Scholar
Chang C-Y, Ting H-C, Liu C-A, Su H-L, Chiou T-W, Lin S-Z, et al. Induced Pluripotent Stem Cell (iPSC)-based neurodegenerative disease models for phenotype recapitulation and drug screening. Molecules. 2020;25(8):2000.
Article CAS PubMed PubMed Central Google Scholar
Holmqvist S, Lehtonen Š, Chumarina M, Puttonen KA, Azevedo C, Lebedeva O, et al. Creation of a library of induced pluripotent stem cells from Parkinsonian patients. NPJ Park Dis. 2016;2:16009.
Article CAS Google Scholar
Ronaldson-Bouchard K, Vunjak-Novakovic G. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell. 2018;22:310–24.
Article CAS PubMed PubMed Central Google Scholar
Okano H, Morimoto S. iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell Stem Cell. 2022;29:189–208.
Article CAS PubMed Google Scholar
Han J, Jeon S, Kim MK, Jeong W, Yoo JJ, Kang H-W. In vitrobreast cancer model with patient-specific morphological features for personalized medicine. Biofabrication. 2022;14(3):034102.
Sequiera GL, Srivastava A, Sareen N, Yan W, Alagarsamy KN, Verma E, et al. Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases. Sci Adv. 2023;8:eabl4370.
Article Google Scholar
Pognan F, Beilmann M, Boonen HCM, Czich A, Dear G, Hewitt P, et al. The evolving role of investigative toxicology in the pharmaceutical industry. Nat Rev Drug Discov. 2023;22:317–35.
Article CAS PubMed PubMed Central Google Scholar
Dilz J, Auge I, Groeneveld K, Reuter S, Mrowka R. A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids. Sci Rep. 2023;13:6167.
Article CAS PubMed PubMed Central Google Scholar
di Val Cervo PR, Besusso D, Conforti P, Cattaneo E. hiPSCs for predictive modelling of neurodegenerative diseases: dreaming the possible. Nat Rev Neurol. 2021;17:381–92.
Article Google Scholar
Corbett JL, Duncan SA. iPSC-derived hepatocytes as a platform for disease modeling and drug discovery. Front Med. 2019;6:265.
Article Google Scholar
Sinnecker D, Goedel A, Laugwitz K-L, Moretti A. Induced pluripotent stem cell-derived cardiomyocytes. Circ Res. 2013;112:961–8.
Article CAS PubMed Google Scholar
Andrysiak K, Stępniewski J, Dulak J. Human-induced pluripotent stem cell-derived cardiomyocytes, 3D cardiac structures, and heart-on-a-chip as tools for drug research. Pflügers Arch - Eur J Physiol. 2021;473:1061–85.
Article CAS Google Scholar
Paik DT, Chandy M, Wu JC. Patient and disease-specific induced pluripotent stem cells for discovery of personalized cardiovascular drugs and therapeutics. Pharmacol Rev. 2020;72:320–42.
Article CAS PubMed PubMed Central Google Scholar
Ko HC, Gelb BD. Concise review: drug discovery in the age of the induced pluripotent stem cell. Stem Cells Transl Med. 2014;3:500–9.
Article CAS PubMed PubMed Central Google Scholar
Li Y, Sallam K, Schwartz PJ, Wu JC. Patient-specific induced pluripotent stem cell-based disease model for pathogenesis studies and clinical pharmacotherapy. Circ Arrhythmia Electrophysiol. 2017;10: e005398.
Article Google Scholar
Thomas D, Shenoy S, Sayed N. Building multi-dimensional induced pluripotent stem cells-based model platforms to assess cardiotoxicity in cancer therapies. Front Pharmacol. 2021;12:607364.
Article CAS PubMed PubMed Central Google Scholar
Sabbagh Seddigh S, Fazlzadeh A, Sabbagh Seddigh S. Evaluation of the Diagnostic Accuracy of Carbon Nanoparticle Suspensions in Sentinel Lymph Node Biopsy of Breast Cancer: A Systematic Review and Meta-analysis. Int J Sci Res Dent Med Sci. 2023;5(3):154–63.
Google Scholar
Hanna J, Cheng AW, Saha K, Kim J, Lengner CJ, Soldner F, et al. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc Natl Acad Sci U S A. 2010;107:9222–7.
Article CAS PubMed PubMed Central Google Scholar
Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018;18:407–18.
Article CAS PubMed Google Scholar
Farshbaf A, Lotfi M, Zare R, Mohtasham N. The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma? Pharmacogenomics J. 2023;23:37–44.
Article CAS PubMed Google Scholar
Meier M-A, Nuciforo S, Coto-Llerena M, Gallon J, Matter MS, Ercan C, et al. Patient-derived tumor organoids for personalized medicine in a patient with rare hepatocellular carcinoma with neuroendocrine differentiation: a case report. Commun Med. 2022;2:80.
Article PubMed PubMed Central Google Scholar
Zhu Z, Hu E, Shen H, Tan J, Zeng S. The functional and clinical roles of liquid biopsy in patient-derived models. J Hematol Oncol. 2023;16:36.
Article PubMed PubMed Central Google Scholar
Werley CA, Boccardo S, Rigamonti A, Hansson EM, Cohen AE. Multiplexed optical sensors in arrayed islands of cells for multimodal recordings of cellular physiology. Nat Commun. 2020;11:3881.
Article PubMed PubMed Central Google Scholar
Valetdinova KR, Malankhanova TB, Zakian SM, Medvedev SP. The cutting edge of disease modeling: synergy of induced pluripotent stem cell technology and genetically encoded biosensors. Biomedicines. 2021;9:960.
Article CAS PubMed PubMed Central Google Scholar
Bhartiya D, Jha N, Tripathi A, Tripathi A. Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging. Front Cell Dev Biol. 2023;4(10):1061022.
Tanaka N, Kato H, Tsuda H, Sato Y, Muramatsu T, Iguchi A, et al. Development of a high-efficacy reprogramming method for generating human induced pluripotent stem (iPS) cells from pathologic and senescent somatic cells. Int J Mol Sci. 2020;21:6764.
Article CAS PubMed PubMed Central Google Scholar
Brunner JW, Lammertse HCA, van Berkel AA, Koopmans F, Li KW, Smit AB, et al. Power and optimal study design in iPSC-based brain disease modelling. Mol Psychiatry. 2023;28:1545–56.
Article PubMed Google Scholar
Geng B, Choi K-H, Wang S, Chen P, Pan X, Dong N, et al. A simple, quick, and efficient CRISPR/Cas9 genome editing method for human induced pluripotent stem cells. Acta Pharmacol Sin. 2020;41:1427–32.
Article CAS PubMed PubMed Central Google Scholar
Nguyen QH, Lukowski SW, Chiu HS, Senabouth A, Bruxner TJC, Christ AN, et al. Single-cell RNA-seq of human induced pluripotent stem cells reveals cellular heterogeneity and cell state transitions between subpopulations. Genome Res. 2018;28:1053–66.
Article CAS PubMed PubMed Central Google Scholar
Teshigawara R, Cho J, Kameda M, Tada T. Mechanism of human somatic reprogramming to iPS cell. Lab Investig. 2017;97:1152–7.
Article CAS PubMed Google Scholar
Matlock AD, Vaibhav V, Holewinski R, Venkatraman V, Dardov V, Manalo D-M, et al. NeuroLINCS proteomics: defining human-derived iPSC proteomes and protein signatures of pluripotency. Sci Data. 2023;10:24.
Article PubMed PubMed Central Google Scholar
Lindoso RS, Kasai-Brunswick TH, Monnerat Cahli G, Collino F, Bastos Carvalho A, de Carvalho ACC, et al. Proteomics in the world of induced pluripotent stem cells. Cells. 2019;8:703.
Article CAS PubMed PubMed Central Google Scholar
Simkin D, Papakis V, Bustos BI, Ambrosi CM, Ryan SJ, Baru V, et al. Homozygous might be hemizygous: CRISPR/Cas9 editing in iPSCs results in detrimental on-target defects that escape standard quality controls. Stem Cell Reports. 2022;17:993–1008.
Article CAS PubMed PubMed Central Google Scholar
Jiang S, Wen N, Li Z, Dube U, Del Aguila J, Budde J, et al. Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP. Transl Psychiatry. 2018;8:265.
Article CAS PubMed PubMed Central Google Scholar
Wann SR, Chi PL, Huang WC, Cheng CC, Te CY. Combination therapy of iPSC-derived conditioned medium with ceftriaxone alleviates bacteria-induced lung injury by targeting the NLRP3 inflammasome. J Cell Physiol. 2022;237:1299–314.
Article CAS PubMed Google Scholar
Schaub NJ, Hotaling NA, Manescu P, Padi S, Wan Q, Sharma R, et al. Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy. J Clin Invest. 2020;130:1010–23.
Article CAS PubMed PubMed Central Google Scholar
Nothdurfter D, Ploner C, Coraça-Huber DC, Wilflingseder D, Müller T, Hermann M, et al. 3D bioprinted, vascularized neuroblastoma tumor environment in fluidic chip devices for precision medicine drug testing. Biofabrication. 2022;14(3):035002.
He Z, Maynard A, Jain A, Gerber T, Petri R, Lin HC, et al. Lineage recording in human cerebral organoids. Nat Methods. 2022;19:90–9.
Article PubMed Google Scholar
Shi J, Ma Y, Zhu J, Chen Y, Sun Y, Yao Y, et al. A review on electroporation-based intracellular delivery. Molecules. 2018;23:3044.
Article PubMed PubMed Central Google Scholar
Huang Y, Xu Y, Lu Y, Zhu S, Guo Y, Sun C, et al. lncRNA Gm10451 regulates PTIP to facilitate iPSCs-derived β-like cell differentiation by targeting miR-338-3p as a ceRNA. Biomaterials. 2019;216: 119266.
Article CAS PubMed Google Scholar
Lanznaster D, Veyrat-Durebex C, Vourc’h P, Andres CR, Blasco H, Corcia P. Metabolomics: A tool to understand the impact of genetic mutations in amyotrophic lateral sclerosis. Genes (Basel). 2020;11:537.
Article CAS PubMed Google Scholar
Nguyen D, Hägg DA, Forsman A, Ekholm J, Nimkingratana P, Brantsing C, et al. Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Sci Rep. 2017;7:658 (http://www.nature.com/articles/s41598-017-00690-y).
Article PubMed PubMed Central Google Scholar
Selevsek N, Caiment F, Nudischer R, Gmuender H, Agarkova I, Atkinson FL, et al. Network integration and modelling of dynamic drug responses at multi-omics levels. Commun Biol. 2020;3:573.
Article CAS PubMed PubMed Central Google Scholar
Osman A, Afify SM, Hassan G, Fu X, Seno A, Seno M. Revisiting cancer stem cells as the origin of cancer-associated cells in the tumor microenvironment: a hypothetical view from the potential of iPSCs. Cancers (Basel). 2020;12:879.
Article CAS PubMed Google Scholar
Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther. 2020;5:1.
Article PubMed PubMed Central Google Scholar
Zhang H, Qin C, An C, Zheng X, Wen S, Chen W, et al. Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer. Mol Cancer. 2021;20:1–22.
Article Google Scholar
Fabre KM, Delsing L, Hicks R, Colclough N, Crowther DC, Ewart L. Utilizing microphysiological systems and induced pluripotent stem cells for disease modeling: a case study for blood brain barrier research in a pharmaceutical setting. Adv Drug Deliv Rev. 2019;140:129–35.
Choi SM, Kim Y, Shim JS, Park JT, Wang RH, Leach SD, et al. Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology. 2013;57:2458–68.
Article CAS PubMed Google Scholar
Lin FK, Chui YL. Generation of induced pluripotent stem cells from mouse cancer cells. Cancer Biother Radiopharm. 2012;27:694–700.
CAS PubMed PubMed Central Google Scholar
Karagiannis P, Kim S-I. iPSC-derived natural killer cells for cancer immunotherapy. Mol Cells. 2021;44:541.
Article CAS PubMed PubMed Central Google Scholar
Prieto-Vila M, Yan T, Calle AS, Nair N, Hurley L, Kasai T, et al. iPSC-derived cancer stem cells provide a model of tumor vasculature. Am J Cancer Res. 2016;6:1906.
CAS PubMed PubMed Central Google Scholar
Suknuntha K, Ishii Y, Hu K, Wang JYJ, Slukvin I. Modeling CML development and drug resistance using iPSC technology. Blood. 2011;118:3767.
Article Google Scholar
Chen X, Wen F, Li Z, Li W, Zhou M, Sun X, et al. Identification of MAEL as a promoter for the drug resistance model of iPSCs derived from T-ALL. Cancer Med. 2022;11:3479–90.
Article CAS PubMed PubMed Central Google Scholar
Tu SM, Guo CC, Chow DS, Zacharias NM. Stem cell theory of cancer: implications for drug resistance and chemosensitivity in cancer care. Cancers (Basel). 2022;14:1548.
Article CAS PubMed Google Scholar
Tobin SC, Kim K. Generating pluripotent stem cells: differential epigenetic changes during cellular reprogramming. FEBS Lett. 2012;586:2874–81.
Article CAS PubMed PubMed Central Google Scholar
Semi K, Yamada Y. Induced pluripotent stem cell technology for dissecting the cancer epigenome. Cancer Sci. 2015;106:1251–6.
Article CAS PubMed PubMed Central Google Scholar
Friedmann-Morvinski D, Verma IM. Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep. 2014;15:244–53.
Article CAS PubMed PubMed Central Google Scholar
Chen L, Kasai T, Li Y, Sugii Y, Jin G, Okada M, et al. A model of cancer stem cells derived from mouse induced pluripotent stem cells. PLoS ONE. 2012;7: e33544.
Article CAS PubMed PubMed Central Google Scholar
Ayuso JM, Ochoa Garrido I. The importance of the tumor microenvironment to understand tumor origin, evolution, and treatment response. Cancers (Basel). 2022;14:1983 (MDPI).
Article PubMed Google Scholar
Draper GM, Panken DJ, Largaespada DA. Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models. Genes Chromosom Cancer. 2023;62(9):493–500.
Article CAS PubMed Google Scholar
Reilly A, Doulatov S. Induced pluripotent stem cell models of myeloid malignancies and clonal evolution. Stem Cell Res. 2021;52: 102195.
Article CAS PubMed PubMed Central Google Scholar
Tu S-M, Zhang M, Wood CG, Pisters LL. Stem cell theory of cancer: origin of tumor heterogeneity and plasticity. Cancers (Basel). 2021;13:4006.
Article CAS PubMed Google Scholar
Doulatov S, Papapetrou EP. Studying clonal evolution of myeloid malignancies using induced pluripotent stem cells. Curr Opin Hematol. 2021;28:50.
Article CAS PubMed PubMed Central Google Scholar
Ferrer AI, Trinidad JR, Sandiford O, Etchegaray J-P, Rameshwar P. Epigenetic dynamics in cancer stem cell dormancy. Cancer Metastasis Rev. 2020;39:721–38.
Article PubMed Google Scholar
Ishida T, Nakao S, Ueyama T, Harada Y, Kawamura T. Metabolic remodeling during somatic cell reprogramming to induced pluripotent stem cells: involvement of hypoxia-inducible factor 1. Inflamm Regen. 2020;40:1–8.
Article Google Scholar
Menendez J, Joven J, Cufí S, Corominas-Faja B, Oliveras-Ferraros C, Cuyàs E, et al. The Warburg effect version 2.0: metabolic reprogramming of cancer stem cells. Cell cycle. 2013;12:1166–79.
Article CAS PubMed PubMed Central Google Scholar
de Jesus BB, Neves BM, Ferreira M, Nóbrega-Pereira S. Strategies for cancer immunotherapy using induced pluripotency stem cells-based vaccines. Cancers (Basel). 2020;12:3581.
Article Google Scholar
Yu Y, Yang G, Huang H, Fu Z, Cao Z, Zheng L, et al. Preclinical models of pancreatic ductal adenocarcinoma: challenges and opportunities in the era of precision medicine. J Exp Clin Cancer Res. 2021;40:1–13.
Article CAS Google Scholar
Jain S, Rick JW, Joshi R, Beniwal A, Spatz J, Chang AC-C, et al. Identification of cancer-associated fibroblasts in glioblastoma and defining their pro-tumoral effects. BioRxiv. 2021;2021–05.
Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582–98.
Article CAS PubMed Google Scholar
Halevy T, Urbach A. Comparing ESC and iPSC—based models for human genetic disorders. J Clin Med. 2014;3:1146–62.
Article PubMed PubMed Central Google Scholar
Fu L, Xu X, Ren R, Wu J, Zhang W, Yang J, et al. Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein Cell. 2016;7:210–21.
Article CAS PubMed PubMed Central Google Scholar
Du J, Campau E, Soragni E, Ku S, Puckett JW, Dervan PB, et al. Role of mismatch repair enzymes in GAA·TTC triplet-repeat expansion in Friedreich ataxia induced pluripotent stem cells. J Biol Chem. 2012;287:29861–72.
Article CAS PubMed PubMed Central Google Scholar
Balani S, Nguyen LV, Eaves CJ. Modeling the process of human tumorigenesis. Nat Commun. 2017;8:15422.
Article CAS PubMed PubMed Central Google Scholar
Giancotti FG. Mechanisms governing metastatic dormancy and reactivation. Cell. 2013;155:750–64.
Article CAS PubMed PubMed Central Google Scholar
Abreu CM, Gama L, Krasemann S, Chesnut M, Odwin-Dacosta S, Hogberg HT, et al. Microglia increase inflammatory responses in iPSC-derived human brainspheres. Front Microbiol. 2018;9:2766.
Article PubMed PubMed Central Google Scholar
Halaidych V, Freund C, van den Hil F, Salvatori DCF, Riminucci M, Mummery CL, et al. Inflammatory responses and barrier function of endothelial cells derived from human induced pluripotent stem cells. Stem Cell Reports. 2018;10:1642–56.
Article CAS PubMed PubMed Central Google Scholar
Butler EB, Zhao Y, Muñoz-Pinedo C, Lu J, Tan M. Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance. Cancer Res. 2013;73:2709–17.
Article CAS PubMed PubMed Central Google Scholar
Huang T, Song X, Xu D, Tiek D, Goenka A, Wu B, et al. Stem cell programs in cancer initiation, progression, and therapy resistance. Theranostics. 2020;10:8721.
Article CAS PubMed PubMed Central Google Scholar
Geijtenbeek TBH. Dendritic Cell Immunotherapy, the Next Step in Cancer Treatment. Multidiscip Cancer Investig. 2017;1:1–2.
Article Google Scholar
Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol. 2021;18:85–100.
Article PubMed Google Scholar
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science (80). 2011;331:1565–70.
Article CAS Google Scholar
Li S, Li Q. A promising approach to iPSC-based cell therapy for diabetic wound treatment: direct lineage reprogramming. Mol Cell Endocrinol. 2014;393:8–15.
Article CAS PubMed Google Scholar
Imparato G, Urciuolo F, Netti PA. Organ on chip technology to model cancer growth and metastasis. Bioengineering. 2022;9:28.
Article CAS PubMed PubMed Central Google Scholar
Galat Y, Perepitchka M, Elcheva I, Iannaccone S, Iannaccone PM, Galat V. iPSC-derived progenitor stromal cells provide new insights into aberrant musculoskeletal development and resistance to cancer in down syndrome. Sci Rep. 2020;10:1–16.
Article Google Scholar
Yamazoe T, Koizumi S, Yamasaki T, Amano S, Tokuyama T, Namba H. Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model. Int J Oncol. 2015;46:147–52.
Article CAS PubMed Google Scholar
Kim M-H, Kino-oka M. Switching between self-renewal and lineage commitment of human induced pluripotent stem cells via cell–substrate and cell–cell interactions on a dendrimer-immobilized surface. Biomaterials. 2014;35:5670–8.
Article CAS PubMed Google Scholar
Pellegrino E, Gutierrez MG. Human stem cell-based models for studying host-pathogen interactions. Cell Microbiol. 2021;23: e13335.
Article CAS PubMed Google Scholar
Cheng YQ, Wang SB, Liu JH, Jin L, Liu Y, Li CY, et al. Modifying the tumour microenvironment and reverting tumour cells: new strategies for treating malignant tumours. Cell Prolif. 2020;53: e12865.
Article PubMed PubMed Central Google Scholar
Wu J, Ocampo A, Belmonte JCI. Cellular metabolism and induced pluripotency. Cell. 2016;166:1371–85.
Article CAS PubMed Google Scholar
Liu G-H, Ding Z, Belmonte JCI. iPSC technology to study human aging and aging-related disorders. Curr Opin Cell Biol. 2012;24:765–74.
Article CAS PubMed Google Scholar
Klein A, Rhinn M, Keyes WM. Cellular senescence and developmental defects. FEBS J. 2023;290(5):1303–13.
Article CAS PubMed Google Scholar
Jiang S-H, Zhang S, Wang H, Xue J-L, Zhang Z-G. Emerging experimental models for assessing perineural invasion in human cancers. Cancer Lett. 2022;535:215610.
Article CAS PubMed Google Scholar
Ryan G. Induced pluripotent stem cell-derived neuroprogenitor cells: a model for studying cannabinoid induced cell signaling. FASEB J. 2020;34:1.
Google Scholar
Hong SG, Winkler T, Wu C, Guo V, Pittaluga S, Nicolae A, et al. Path to the clinic: assessment of iPSC-based cell therapies in vivo in a nonhuman primate model. Cell Rep. 2014;7:1298–309.
Article CAS PubMed PubMed Central Google Scholar
Kawamoto H, Masuda K, Nagano S. Regeneration of antigen-specific T cells by using induced pluripotent stem cell (iPSC) technology. Int Immunol. 2021;33:827–33.
Article CAS PubMed Google Scholar
Vermilyea SC, Guthrie S, Meyer M, Smuga-Otto K, Braun K, Howden S, et al. Induced pluripotent stem cell-derived dopaminergic neurons from adult common marmoset fibroblasts. Stem Cells Dev. 2017;26:1225–35.
Article CAS PubMed PubMed Central Google Scholar
Escribá R, Ferrer-Lorente R, Raya Á. Inborn errors of metabolism: Lessons from iPSC models. Rev Endocr Metab Disord. 2021;22:1189–200.
Article PubMed PubMed Central Google Scholar
Zheng H, Harcum SW, Pei J, Xie W. Stochastic biological system-of-systems modelling for iPSC culture. arXiv Prepr arXiv230517787. 2023;
Borbaran-Bravo N, Arreba-Tutusaus P, Ritter MU, Nasri M, Klimiankou M, Skokowa J. Regenerative medicine meets translational oncology: modeling leukemic bone marrow niche. Cell Reports Med. 2022;3: 100724.
Article Google Scholar
Roh J, Kim S, Cheong J-W, Jeon S-H, Kim H-K, Kim MJ, et al. Erythroid Differentiation of Induced Pluripotent Stem Cells Co-cultured with OP9 Cells for Diagnostic Purposes. Ann Lab Med. 2022;42:457–66.
Article CAS PubMed PubMed Central Google Scholar
Sharma P, Kumar P, Sharma R. Natural killer cells-their role in tumour immunosurveillance. J Clin Diagn Res. 2017;11:BE01.
PubMed PubMed Central Google Scholar
Bruttel VS, Wischhusen J. Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune escape? Front Immunol. 2014;5:360.
Article PubMed PubMed Central Google Scholar
Lin Y-C, Murayama Y, Hashimoto K, Nakamura Y, Lin C-S, Yokoyama KK, et al. Role of tumor suppressor genes in the cancer-associated reprogramming of human induced pluripotent stem cells. Stem Cell Res Ther. 2014;5:1–9.
Article Google Scholar
Liu M, Guo F. Recent updates on cancer immunotherapy. Precis Clin Med. 2018;1:65–74.
Article PubMed PubMed Central Google Scholar
Ural EE, Toomajian V, Hoque Apu E, Veletic M, Balasingham I, Ashammakhi N, et al. Visualizing extracellular vesicles and their function in 3D tumor microenvironment models. Int J Mol Sci. 2021;22:4784.
Article CAS PubMed PubMed Central Google Scholar
Sakowski SA, Chen KS. Stem cell therapy for central nervous system disorders: Metabolic interactions between transplanted cells and local microenvironments. Neurobiol Dis. 2022;173: 105842.
Article CAS PubMed PubMed Central Google Scholar
Vlashi E, Pajonk F. Cancer stem cells, cancer cell plasticity and radiation therapy. Semin Cancer Biol. 2015;31:28–35.
Article CAS PubMed Google Scholar
Suh Y, Lee S-J. Radiation treatment and cancer stem cells. Arch Pharm Res. 2015;38:408–13.
Article CAS PubMed Google Scholar
Hayat H, Hayat H, Dwan BF, Gudi M, Bishop JO, Wang P. A concise review: the role of stem cells in cancer progression and therapy. Onco Targets Ther. 2021;14:2761.
Article PubMed PubMed Central Google Scholar
Boussommier-Calleja A. In vitro models of cancer. Bioeng Innov Solut Cancer. 2020;273–325
Horvath P, Aulner N, Bickle M, Davies AM, Del NE, Ebner D, et al. Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov. 2016;15:751–69.
Article CAS PubMed Google Scholar
Vander Heiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov. 2011;10:671–84.
Article CAS PubMed Google Scholar
Farrugia MK, Vanderbilt DB, Salkeni MA, Ruppert JM. Kruppel-like pluripotency factors as modulators of cancer cell therapeutic responses. Cancer Res. 2016;76:1677–82.
Article CAS PubMed PubMed Central Google Scholar
Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009;138:822–9.
Article CAS PubMed Google Scholar
Bellin M, Marchetto MC, Gage FH, Mummery CL. Induced pluripotent stem cells: The new patient? Nat Rev Mol Cell Biol. 2012;13:713–26.
Article PubMed Google Scholar
Kim HJ, Jeong J, Park S, Jin Y-W, Lee S-S, Lee SB, et al. Establishment of hepatocellular cancer induced pluripotent stem cells using a reprogramming technique. Gut Liver. 2017;11:261–9.
Article CAS PubMed Google Scholar
Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008;105:2883–8.
Article CAS PubMed PubMed Central Google Scholar
Sommer CA, Capilla A, Molina-Estevez FJ, Gianotti-Sommer A, Skvir N, Caballero I, et al. Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells. PLoS One. 2018;13:e0200657.
Article PubMed PubMed Central Google Scholar
Smith RC, Tabar V. Constructing and deconstructing cancers using human pluripotent stem cells and organoids. Cell Stem Cell. 2019;24:12–24.
Article CAS PubMed Google Scholar
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.
Article CAS PubMed Google Scholar
Castro-Pérez E, Rodríguez CI, Mikheil D, Siddique S, McCarthy A, Newton MA, et al. Melanoma progression inhibits pluripotency and differentiation of melanoma-derived iPSCs produces cells with neural-like mixed dysplastic phenotype. Stem Cell Rep. 2019;13:177–92.
Article Google Scholar
Gandre-Babbe S, Paluru P, Aribeana C, Chou ST, Bresolin S, Lu L, et al. Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia. Blood. 2013;121:4925–9.
Article CAS PubMed PubMed Central Google Scholar
Wang L, Cao J, Wang Y, Lan T, Liu L, Wang W, et al. Immunogenicity and functional evaluation of iPSC-derived organs for transplantation. Cell Discov. 2015;1:15015.
Article PubMed PubMed Central Google Scholar
Sharkis SJ, Jones RJ, Civin C, Jang YY. Pluripotent stem cell–based cancer therapy: Promise and challenges. Sci Transl Med. 2012;4:127ps9.
Article PubMed PubMed Central Google Scholar
Oh Y, Jang J. Directed differentiation of pluripotent stem cells by transcription factors. Mol Cells. 2019;42:200.
CAS PubMed PubMed Central Google Scholar
Ramos-Mejia V, Fraga MF, Menendez P. iPSCs from cancer cells: challenges and opportunities. Trends Mol Med. 2012;18:245–7.
Article CAS PubMed Google Scholar
Sagar J, Chaib B, Sales K, Winslet M, Seifalian A. Role of stem cells in cancer therapy and cancer stem cells: a review. Cancer Cell Int. 2007;7:1–11.
Article Google Scholar
Li Y-R, Dunn ZS, Yu Y, Li M, Wang P, Yang L. Advancing cell-based cancer immunotherapy through stem cell engineering. Cell Stem Cell. 2023;30(5):592–610.
Article CAS PubMed Google Scholar
Cai S, Hou J, Fujino M, Zhang Q, Ichimaru N, Takahara S, et al. iPSC-derived regulatory dendritic cells inhibit allograft rejection by generating alloantigen-specific regulatory T cells. Stem Cell Reports. 2017;8:1174–89.
Article CAS PubMed PubMed Central Google Scholar
Fukushima S, Miyashita A, Kuriyama H, Kimura T, Mizuhashi S, Kubo Y, et al. Future prospects for cancer immunotherapy using induced pluripotent stem cell-derived dendritic cells or macrophages. Exp Dermatol. 2023;32:290–6.
Article CAS PubMed Google Scholar
Paijens ST, Vledder A, de Bruyn M, Nijman HW. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol. 2021;18:842–59.
Article CAS PubMed Google Scholar
Yamamoto TN, Kishton RJ, Restifo NP. Developing neoantigen-targeted T cell–based treatments for solid tumors. Nat Med. 2019;25:1488–99.
Article CAS PubMed Google Scholar
Sachamitr P, Hackett S, Fairchild PJ. Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy. Front Immunol. 2014;5:176.
Article PubMed PubMed Central Google Scholar
Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al. Cancer statistics, 2020: report from national cancer registry programme. India JCO Glob Oncol. 2020;6:1063–75.
Article PubMed Google Scholar
Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2022;23:74–88.
Article CAS PubMed Google Scholar
Crosas-Molist E, Samain R, Kohlhammer L, Orgaz JL, George SL, Maiques O, et al. Rho GTPase signaling in cancer progression and dissemination. Physiol Rev. 2022;102:455–510.
Article CAS PubMed Google Scholar
Zisi A, Bartek J, Lindström MS. Targeting ribosome biogenesis in cancer: lessons learned and way forward. Cancers (Basel). 2022;14:2126.
Article CAS PubMed Google Scholar
Wang L, Yu L, Shi J, Li F, Zhang C, Xu H, et al. Functional regulations between genetic alteration-driven genes and drug target genes acting as prognostic biomarkers in breast cancer. Sci Rep. 2022;12:10641.
Article CAS PubMed PubMed Central Google Scholar
Garnis C, Buys TPH, Lam WL. Genetic alteration and gene expression modulation during cancer progression. Mol Cancer. 2004;3:1–23.
Article Google Scholar
Viner-Breuer R, Yilmaz A, Benvenisty N, Goldberg M. The essentiality landscape of cell cycle related genes in human pluripotent and cancer cells. Cell Div. 2019;14:1–13.
Article Google Scholar
Ythier D, Larrieu D, Brambilla C, Brambilla E, Pedeux R. The new tumor suppressor genes ING: genomic structure and status in cancer. Int J cancer. 2008;123:1483–90.
Article CAS PubMed Google Scholar
Schnekenburger M, Florean C, Dicato M, Diederich M. Epigenetic alterations as a universal feature of cancer hallmarks and a promising target for personalized treatments. Curr Top Med Chem. 2016;16:745–76.
Article CAS PubMed Google Scholar
Kanwal R, Gupta S. Epigenetic modifications in cancer. Clin Genet. 2012;81:303–11.
Article CAS PubMed Google Scholar
Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, et al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther. 2019;4:62.
Article PubMed PubMed Central Google Scholar
Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 2005;435:1262–6.
Article CAS PubMed Google Scholar
Fahrner JA, Eguchi S, Herman JG, Baylin SB. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 2002;62:7213–8.
CAS PubMed Google Scholar
Ben-Porath I, Cedar H. Epigenetic crosstalk. Mol Cell. 2001;8:933–5.
Article CAS PubMed Google Scholar
Toraño EG, García MG, Fernández-Morera JL, Niño-García P, Fernández AF. The impact of external factors on the epigenome: in utero and over lifetime. Biomed Res Int. 2016;2016:2568635.
Article PubMed PubMed Central Google Scholar
Choi JD, Lee J-S. Interplay between epigenetics and genetics in cancer. Genomics Inform. 2013;11:164–73.
Article PubMed PubMed Central Google Scholar
Fernández AF, Toraño EG, Urdinguio RG, Lana AG, Fernández IA, Fraga MF. The epigenetic basis of adaptation and responses to environmental change: perspective on human reproduction. Reprod Sci Anim Conserv Prog Prospect. 2014;753:97–117.
Google Scholar
Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21:243.
Article PubMed PubMed Central Google Scholar
Keyes MK, Jang H, Mason JB, Liu Z, Crott JW, Smith DE, et al. Older age and dietary folate are determinants of genomic and p16-specific DNA methylation in mouse colon. J Nutr. 2007;137:1713–7.
Article CAS PubMed Google Scholar
Verma M, Kumar V. Epigenetic biomarkers in colorectal cancer. Mol Diagn Ther. 2017;21:153–65.
Article CAS PubMed Google Scholar
Kalani A, Kamat PK, Givvimani S, Brown K, Metreveli N, Tyagi SC, et al. Nutri-epigenetics ameliorates blood–brain barrier damage and neurodegeneration in hyperhomocysteinemia: role of folic acid. J Mol Neurosci. 2014;52:202–15.
Article CAS PubMed PubMed Central Google Scholar
Huber K, Doyon G, Plaks J, Fyne E, Mellors JW, Sluis-Cremer N. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J Biol Chem. 2011;286:22211–8.
Article CAS PubMed PubMed Central Google Scholar
Cabarcas SM, Mathews LA, Farrar WL. The cancer stem cell niche—there goes the neighborhood? Int J cancer. 2011;129:2315–27.
Article CAS PubMed PubMed Central Google Scholar
Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14:275–91.
Article CAS PubMed Google Scholar
Dreesen O, Brivanlou AH. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. 2007;3:7–17.
Article CAS PubMed Google Scholar
Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev cancer. 2004;4:937–47.
Article CAS PubMed Google Scholar
Grant S. Cotargeting survival signaling pathways in cancer. J Clin Invest. 2008;118:3003–6.
Article CAS PubMed PubMed Central Google Scholar
Skoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Bosn J basic Med Sci. 2018;18:8.
Article CAS PubMed PubMed Central Google Scholar
Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V. Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med. 2017;6:2115–25.
Article PubMed PubMed Central Google Scholar
Talukdar S, Bhoopathi P, Emdad L, Das S, Sarkar D, Fisher PB. Dormancy and cancer stem cells: an enigma for cancer therapeutic targeting. Adv Cancer Res. 2019;141:43–84.
Article CAS PubMed Google Scholar
Kristensen LS, Jakobsen T, Hager H, Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022;19:188–206.
Article CAS PubMed Google Scholar
Nourian Dehkordi A, Mirahmadi Babaheydari F, Chehelgerdi M, Raeisi Dehkordi S. Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Therapy. 2019;10(1):1–20.
Article Google Scholar

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Acknowledgements

We would like to thank from the Novin Genome (NG) Lab, Shahrekord branch, Research and Development Center for Biotechnology in southwest Iran for their kindly cooperation.

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The authors declare that no funding was received for the research.

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Authors and Affiliations

Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran
Matin Chehelgerdi, Fereshteh Behdarvand Dehkordi, Mohammad Chehelgerdi, Hamidreza Kabiri & Saber Kabiri
Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
Matin Chehelgerdi, Fereshteh Behdarvand Dehkordi, Mohammad Chehelgerdi, Hamidreza Kabiri & Saber Kabiri
College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
Hosein Salehian-Dehkordi
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
Mohammad Abdolvand, Anoosha Niazmand, Sara Feizbakhshan & Tayebeh Ranjbarnejad
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar-Jereeb Street, Isfahan, 81746-73441, Iran
Sharareh Salmanizadeh
Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Mohsen Rashidi
The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Mohsen Rashidi
Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia
Saba Ahmadi
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
Nasimeh Vatandoost

Authors

Matin Chehelgerdi
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Fereshteh Behdarvand Dehkordi
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Mohammad Chehelgerdi
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Hamidreza Kabiri
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Hosein Salehian-Dehkordi
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Mohammad Abdolvand
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Sharareh Salmanizadeh
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Mohsen Rashidi
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Anoosha Niazmand
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Saba Ahmadi
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Sara Feizbakhshan
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Saber Kabiri
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Nasimeh Vatandoost
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Tayebeh Ranjbarnejad
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Contributions

MCH, HK, SK, MA, SHS, AN, SF and MCH, searching, MCH: analyzing, writing- original draft preparation. MCH: reviewing, editing. MCH.: software, validation. MCH: writing, reviewing. MCH and MCH: reviewing, editing, MCH: reviewing, editing and supervision. All authors approved the final version of the manuscript.

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Correspondence to Mohammad Chehelgerdi.

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Chehelgerdi, M., Behdarvand Dehkordi, F., Chehelgerdi, M. et al. Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy. Mol Cancer 22, 189 (2023). https://doi.org/10.1186/s12943-023-01873-0

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Received: 04 July 2023
Accepted: 27 September 2023
Published: 28 November 2023
DOI: https://doi.org/10.1186/s12943-023-01873-0