CHU Montpellier, SAFE-IPS Reprogramming Platform, Institute of Research in Biotherapy, Montpellier, F34000 France.
Curr Gene Ther. 2013 Apr;13(2):93-8. doi: 10.2174/1566523211313020003.
Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research and medical applications. iPSCs were initially favorably compared to ESCs. This view was first based on ethical arguments (the generation of iPSCs does not require the destruction of an embryo) and on immunological reasons (it is easier to derive patient HLA-matched iPSCs than ESCs). However, several reports suggest that iPSCs might be characterized by higher occurrence of epigenetic and genetic aberrations than ESCs as a consequence of the reprogramming process. We focus here on the DNA integrity of pluripotent stem cells and examine the three main sources of genomic abnormalities in iPSCs: (1) genomic variety of the parental cells, (2) cell reprogramming, and (3) in vitro cell culture. Recent reports claim that it is possible to generate mouse or human iPSC lines with a mutation level similar to that of the parental cells, suggesting that "genome-friendly" reprogramming techniques can be developed. The issue of iPSC DNA integrity clearly highlights the crucial need of guidelines to define the acceptable level of genomic integrity of pluripotent stem cells for biomedical applications. We discuss here the main issues that such guidelines should address.
诱导多能干细胞 (iPSCs) 和胚胎干细胞 (ESCs) 是两种多能干细胞，它们在生物医学研究和医学应用中具有巨大的潜力。iPSCs 最初被认为优于 ESCs。这种观点最初基于伦理论据（生成 iPSCs 不需要破坏胚胎）和免疫学原因（与 ESCs 相比，更容易获得患者 HLA 匹配的 iPSCs）。然而，几项报告表明，iPSCs 可能由于重编程过程而表现出比 ESCs 更高的表观遗传和遗传异常发生率。我们在这里关注多能干细胞的 DNA 完整性，并检查 iPSCs 中三种主要的基因组异常来源：（1）亲本细胞的基因组多样性，（2）细胞重编程，和（3）体外细胞培养。最近的报告声称，可以生成具有与亲本细胞相似突变水平的小鼠或人类 iPSC 系，这表明可以开发“对基因组友好”的重编程技术。iPSC DNA 完整性的问题清楚地突出了为生物医学应用定义多能干细胞可接受的基因组完整性水平制定指南的关键需求。我们在这里讨论了此类指南应解决的主要问题。
