Stem Cell Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Genes Cells. 2009 Dec;14(12):1395-404. doi: 10.1111/j.1365-2443.2009.01356.x. Epub 2009 Nov 13.
Practical clinical applications for current induced pluripotent stem cell (iPSC) technologies are hindered by very low generation efficiencies. Here, we demonstrate that newborn human (h) and mouse (m) extra-embryonic amnion (AM) and yolk-sac (YS) cells, in which endogenous KLF4/Klf4, c-MYC/c-Myc and RONIN/Ronin are expressed, can be reprogrammed to hiPSCs and miPSCs with efficiencies for AM cells of 0.02% and 0.1%, respectively. Both hiPSC and miPSCs are indistinguishable from embryonic stem cells in colony morphology, expression of pluripotency markers, global gene expression profile, DNA methylation status of OCT4 and NANOG, teratoma formation and, in the case of miPSCs, generation of germline transmissible chimeric mice. As copious amounts of human AM cells can be collected without invasion, and stored long term by conventional means without requirement for in vitro culture, they represent an ideal source for cell banking and subsequent 'on demand' generation of hiPSCs for personal regenerative and pharmaceutical applications.
目前诱导多能干细胞（iPSC）技术的实际临床应用受到非常低的生成效率的阻碍。在这里，我们证明，表达内源性 KLF4/Klf4、c-MYC/c-Myc 和 RONIN/Ronin 的新生人类（h）和小鼠（m）胚胎外羊膜（AM）和卵黄囊（YS）细胞可以被重编程为 hiPSC 和 miPSC，AM 细胞的效率分别为 0.02%和 0.1%。无论是 hiPSC 还是 miPSC，在集落形态、多能性标志物的表达、全基因组表达谱、OCT4 和 NANOG 的 DNA 甲基化状态、畸胎瘤形成，以及在 miPSC 的情况下，生成种系可传播的嵌合小鼠方面，都与胚胎干细胞无法区分。由于可以大量收集人类 AM 细胞而无需侵袭，并且可以通过常规手段长期储存而无需体外培养，因此它们是细胞库的理想来源，并且可以随后按需生成 hiPSC，用于个人再生和药物应用。
