Oliveri Roberto S
The Juliane Marie Center for Children, Women, and Reproduction, Laboratory of Reproductive Biology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Regen Med. 2007 Sep;2(5):795-816. doi: 10.2217/17460751.2.5.795.
Ever since the derivation of the first human embryonic stem cell line, hopes have persisted for the treatment of a wide range of cellular degenerative diseases. However, significant immuno-incompatibility between donor cells and recipient patients remains an unsolved challenge. Currently, three main strategies are investigated in humans to create autologous pluripotent stem cells: somatic cell nuclear transfer, cell fusion and cell extract incubation. All methods exploit the fact that a somatic genome is amenable to epigenetic dedifferentiation into a more plastic state, presumably through direct exposure to and manipulation by heterologous transcriptional factors. Epigenetic reprogramming includes profound modifications of chromatin structure, but the responsible mechanisms that work in toti- and pluripotent cells remain largely unknown. This review presents a brief introduction to stem cell terminology and epigenetics, followed by a critical examination of the predominant methodologies involved. Finally, the search for specific reprogramming factors is discussed, and obstacles for the clinical implementation of reprogrammed cells are addressed.
自首个人类胚胎干细胞系问世以来，人们一直寄希望于利用其治疗多种细胞退行性疾病。然而，供体细胞与受体患者之间严重的免疫不相容性仍是一个尚未解决的难题。目前，在人体中研究了三种主要策略来创建自体多能干细胞：体细胞克隆、细胞融合和细胞提取物孵育。所有这些方法都利用了这样一个事实，即体细胞基因组大概通过直接暴露于异源转录因子并受其操纵，从而易于发生表观遗传去分化，进入更具可塑性的状态。表观遗传重编程包括染色质结构的深刻改变，但在全能和多能细胞中起作用的相关机制仍 largely unknown。本文首先简要介绍干细胞术语和表观遗传学，随后对主要涉及的方法进行批判性审视。最后，讨论了寻找特定重编程因子的问题，并阐述了重编程细胞临床应用的障碍。 （注：原文中“largely unknown”这里按字面意思翻译为“很大程度上未知”，但结合语境可能表述不太准确，可根据实际情况调整，比如“仍不清楚”等。）
