Tissue Engineering Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Amagasaki, Hyogo, Japan.
Tissue Eng Part A. 2010 Jul;16(7):2197-206. doi: 10.1089/ten.TEA.2009.0747.
Human adipose-derived stem cells (hASCs) are ubiquitous, plentiful, and easily/safely obtainable cells derived from adipose tissue, regardless of the age and sex of the donor. However, the hASCs have limited proliferative and differentiation capabilities. In this study, we examined whether induced pluripotent stem cells (iPSCs) could be generated from hASCs. We transduced hASCs with three human transcription factors (OCT3/4, SOX2, and KLF4), and found that they formed human embryonic stem cell (ESC)-like colonies. Importantly, we did not transduce c-MYC, which is usually utilized to generate iPSCs but is considered an oncogene. These colonies expressed human ESC-specific surface antigens (stage-specific embryonic antigens SSEA-3 and SSEA-4, and tumor-related antigens TRA-1-60 and TRA-1-81), endogenous transcription factors (OCT3/4, NANOG, and SOX2), and undifferentiated human ESC marker genes (REX1, UTF1, GDF3, DPPA2, DPPA4, and DPPA5). Further, the colonies were able to differentiate into the three germ layers both in vitro and in vivo. These results show that human iPSCs can be generated by the transduction of three factors (OCT3/4, SOX2, and KLF4) into hASCs.
人类脂肪来源的干细胞（hASCs）是普遍存在的、丰富的，并且可以从脂肪组织中轻易/安全地获得，无论供体的年龄和性别如何。然而，hASCs 的增殖和分化能力有限。在本研究中，我们研究了是否可以从 hASCs 中产生诱导多能干细胞（iPSCs）。我们将三种人类转录因子（OCT3/4、SOX2 和 KLF4）转导到 hASCs 中，发现它们形成了类似于人类胚胎干细胞（ESC）的集落。重要的是，我们没有转导 c-MYC，c-MYC 通常用于产生 iPSCs，但被认为是一种致癌基因。这些集落表达人类 ESC 特异性表面抗原（阶段特异性胚胎抗原 SSEA-3 和 SSEA-4，以及肿瘤相关抗原 TRA-1-60 和 TRA-1-81）、内源性转录因子（OCT3/4、NANOG 和 SOX2）和未分化的人类 ESC 标记基因（REX1、UTF1、GDF3、DPPA2、DPPA4 和 DPPA5）。此外，这些集落能够在体外和体内分化为三个胚层。这些结果表明，通过将三种因子（OCT3/4、SOX2 和 KLF4）转导到 hASCs 中可以产生人类 iPSCs。
