Department of Health Science, University of Milan, via A di Rudinì 8, 20142 Milan, Italy.
Cells. 2021 Jun 11;10(6):1470. doi: 10.3390/cells10061470.
The production of induced pluripotent stem cells (iPSCs) represent a breakthrough in regenerative medicine, providing new opportunities for understanding basic molecular mechanisms of human development and molecular aspects of degenerative diseases. In contrast to human embryonic stem cells (ESCs), iPSCs do not raise any ethical concerns regarding the onset of human personhood. Still, they present some technical issues related to immune rejection after transplantation and potential tumorigenicity, indicating that more steps forward must be completed to use iPSCs as a viable tool for in vivo tissue regeneration. On the other hand, cell source origin may be pivotal to iPSC generation since residual epigenetic memory could influence the iPSC phenotype and transplantation outcome. In this paper, we first review the impact of reprogramming methods and the choice of the tissue of origin on the epigenetic memory of the iPSCs or their differentiated cells. Next, we describe the importance of induction methods to determine the reprogramming efficiency and avoid integration in the host genome that could alter gene expression. Finally, we compare the significance of the tissue of origin and the inter-individual genetic variation modification that has been lightly evaluated so far, but which significantly impacts reprogramming.
诱导多能干细胞（iPSCs）的产生代表了再生医学的突破，为理解人类发育的基本分子机制和退行性疾病的分子方面提供了新的机会。与人类胚胎干细胞（ESCs）不同，iPSCs 不会引起任何关于人类人格开始的伦理问题。然而，它们在移植后的免疫排斥和潜在的致瘤性方面存在一些技术问题，这表明必须完成更多的步骤，才能将 iPSCs 用作体内组织再生的可行工具。另一方面，细胞来源可能对 iPSC 的产生至关重要，因为残留的表观遗传记忆可能会影响 iPSC 的表型和移植结果。在本文中，我们首先回顾了重编程方法和组织起源对 iPSCs 或其分化细胞的表观遗传记忆的影响。接下来，我们描述了诱导方法的重要性，以确定重编程效率并避免整合到宿主基因组中，这可能会改变基因表达。最后，我们比较了组织来源和个体间遗传变异修饰的重要性，到目前为止，后者虽然已经得到了一定程度的评估，但对重编程的影响却非常显著。
