Centre for Stem Cell Biology, School of Biological Sciences, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK; Steering Committee, International Stem Cell Initiative.
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel; Steering Committee, International Stem Cell Initiative.
Cell Stem Cell. 2022 Dec 1;29(12):1624-1636. doi: 10.1016/j.stem.2022.11.006.
It is well established that human pluripotent stem cells (hPSCs) can acquire genetic and epigenetic changes during culture in vitro. Given the increasing use of hPSCs in research and therapy and the vast expansion in the number of hPSC lines available for researchers, the International Society for Stem Cell Research has recognized the need to reassess quality control standards for ensuring the genetic integrity of hPSCs. Here, we summarize current knowledge of the nature of recurrent genetic and epigenetic variants in hPSC culture, the methods for their detection, and what is known concerning their effects on cell behavior in vitro or in vivo. We argue that the potential consequences of low-level contamination of cell therapy products with cells bearing oncogenic variants are essentially unknown at present. We highlight the key challenges facing the field with particular reference to safety assessment of hPSC-derived cellular therapeutics.
众所周知，人类多能干细胞（hPSCs）在体外培养过程中会获得遗传和表观遗传变化。鉴于 hPSCs 在研究和治疗中的应用日益增多，以及可用于研究人员的 hPSC 系数量的大量增加，国际干细胞研究学会已经认识到需要重新评估质量控制标准，以确保 hPSCs 的遗传完整性。在这里，我们总结了 hPSC 培养中反复出现的遗传和表观遗传变异的性质、检测方法以及已知的这些变异对细胞在体外或体内行为的影响。我们认为，目前对于携带致癌变异的细胞污染细胞治疗产品的潜在后果基本上是未知的。我们特别强调了该领域面临的关键挑战，特别是针对 hPSC 衍生细胞治疗产品的安全性评估。
