Inducing iPSCs to escape the dish.

Inducing iPSCs to escape the dish.
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DOI:
10.1016/j.stem.2011.07.006
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发表时间:
2011-08-05
期刊:
影响因子:
23.9
通讯作者:
Knoepfler, Paul S.
Knoepfler, Paul S.
中科院分区:
医学1区
文献类型:
--
作者:
Barrilleaux, Bonnie;Knoepfler, Paul S.

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诱导多能干细胞(iPSC)为自体细胞疗法带来了巨大的希望,但将iPSC转化为床边仍然存在重大障碍。例如,最近的一篇论文提出了对iPSC的假定自体移植潜力的担忧,该论文表明iPSC衍生的畸胎瘤被同基因宿主排斥。此外,重编程过程可以改变基因组和表观基因组状态,因此此时的关键目标是确定这些变化的临床相关性,并最大限度地减少那些被证明是有害的。最后,到目前为止,很少有研究在临床相关的移植情况下检查iPSCs的功效和致瘤性,这是FDA的基本要求。我们讨论了这些障碍的潜在解决方案,为iPSCs“跳菜”并成为有用的疗法提供路线图。
Induced pluripotent stem cells (iPSCs) hold great promise for autologous cell therapies, but significant roadblocks remain to translating iPSCs to the bedside. For example, concerns about the presumed autologous transplantation potential of iPSCs have been raised by a recent paper demonstrating that iPSC-derived teratomas were rejected by syngeneic hosts. Additionally, the reprogramming process can alter genomic and epigenomic states, so a key goal at this point is to determine the clinical relevance of these changes and minimize those that prove to be deleterious. Finally, thus far few studies have examined the efficacy and tumorigenicity of iPSCs in clinically relevant transplantation scenarios, an essential requirement for the FDA. We discuss potential solutions to these hurdles to provide a roadmap for iPSCs to “jump the dish” and become useful therapies.
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