Wolf Don P, Morey Robert, Kang Eunju, Ma Hong, Hayama Tomonari, Laurent Louise C, Mitalipov Shoukhrat
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, Oregon, USA.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
Stem Cells. 2017 Jan;35(1):26-34. doi: 10.1002/stem.2496. Epub 2016 Sep 27.
Embryonic stem cells (ESC) hold promise for the treatment of human medical conditions but are allogeneic. Here, we consider the differences between autologous pluripotent stem cells produced by nuclear transfer (NT-ESCs) and transcription factor-mediated, induced pluripotent stem cells (iPSCs) that impact the desirability of each of these cell types for clinical use. The derivation of NT-ESCs is more cumbersome and requires donor oocytes; however, the use of oocyte cytoplasm as the source of reprogramming factors is linked to a key advantage of NT-ESCs-the ability to replace mutant mitochondrial DNA in a patient cell (due to either age or inherited disease) with healthy donor mitochondria from an oocyte. Moreover, in epigenomic and transcriptomic comparisons between isogenic iPSCs and NT-ESCs, the latter produced cells that more closely resemble bona fide ESCs derived from fertilized embryos. Thus, although NT-ESCs are more difficult to generate than iPSCs, the ability of somatic cell nuclear transfer to replace aged or diseased mitochondria and the closer epigenomic and transcriptomic similarity between NT-ESCs and bona fide ESCs may make NT-ESCs superior for future applications in regenerative medicine. Stem Cells 2017;35:26-34.
胚胎干细胞（ESC）有望用于治疗人类疾病，但它们是异体的。在此，我们探讨了通过核移植产生的自体多能干细胞（NT-ESC）与转录因子介导的诱导多能干细胞（iPSC）之间的差异，这些差异影响了每种细胞类型在临床应用中的可取性。NT-ESC的获取更为繁琐，需要供体卵母细胞；然而，将卵母细胞细胞质用作重编程因子的来源与NT-ESC的一个关键优势相关——能够用来自卵母细胞的健康供体线粒体替换患者细胞中突变的线粒体DNA（由于年龄或遗传疾病）。此外，在同基因iPSC和NT-ESC的表观基因组和转录组比较中，后者产生的细胞与源自受精卵的真正ESC更为相似。因此，尽管NT-ESC比iPSC更难生成，但体细胞核移植替换老化或患病线粒体的能力以及NT-ESC与真正ESC之间更接近的表观基因组和转录组相似性可能使NT-ESC在未来再生医学应用中更具优势。《干细胞》2017年；35卷：26 - 34页。
