Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells
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Updated: Jun 25, 2025

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
Published on: February 2, 2024
Ying-Chu Lin1, Cha-Chien Ku2,3,4, Kenly Wuputra2,3,4,5
1School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Abstract:
The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.
Insights
Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) offers regenerative medicine potential. Research focuses on reducing iPSC tumorigenicity and enhancing safety for clinical applications.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Biotechnology
Background:
- Somatic cell reprogramming to pluripotent stem cells holds promise for tissue regeneration and transplantation.
- Induced pluripotent stem cells (iPSCs) express embryonic stem cell markers and can differentiate into various cell types.
- Challenges include tumorigenicity, immunogenicity, and cell population heterogeneity, hindering therapeutic use.
Purpose of the Study:
- To review recent advancements in reducing the tumorigenic risk of iPSCs and iPSC-derived organoids.
- To highlight strategies for increasing the safety of iPSC preparation and therapeutic application.
- To explore chemical induction of iPSCs as a safe, clinical-grade manufacturing strategy.
Main Methods:
- Review of recent scientific literature on iPSC generation and safety.
- Analysis of chemical induction methods for iPSC generation from human fibroblasts.
- Examination of strategies to mitigate genetic and epigenetic alterations associated with tumorigenicity.
Main Results:
- Chemical induction offers a safe, easy, and clinical-grade manufacturing strategy for iPSCs.
- Progress has been made in decreasing the tumorigenic potential of iPSCs and iPSC-derived organoids.
- Understanding genetic and epigenetic factors influencing stemness gene mutations is crucial.
Conclusions:
- iPSC technology is advancing towards safer and more effective regenerative therapies.
- Chemical induction represents a promising route for clinical translation of reprogramming therapy.
- Continued research is essential to overcome safety concerns and maximize therapeutic benefits of iPSCs.
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