Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor–AB and 5-azacytidine into multipotent stem cells with stromal cell characteristics. We have now optimized culture conditions to reprogram human adipocytes into induced multipotent stem (iMS) cells and characterized their molecular and functional properties. Although the basal transcriptomes of adipocyte-derived iMS cells and adipose tissue–derived mesenchymal stem cells were similar, there were changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to muscle, bone, cartilage, and blood vessels, with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibers without ectopic tissue formation. Together, human adipocyte–derived iMS cells regenerate tissues in a context-dependent manner without ectopic or neoplastic growth.

终末分化的小鼠骨细胞和脂肪细胞可以使用血小板衍生的生长因子-AB 和 5-氮杂胞苷重编程为具有基质细胞特征的多能干细胞。我们现在优化了培养条件，将人类脂肪细胞重新编程为诱导多能干 (iMS) 细胞，并表征了它们的分子和功能特性。尽管脂肪细胞来源的 iMS 细胞和脂肪组织来源的间充质干细胞的基础转录组相似，但顺式调节区域的组蛋白修饰和 CpG 甲基化发生了变化，这与为组织发育和分化做好准备的表观遗传景观一致。在非特异性组织损伤异种移植模型中，iMS 细胞直接作用于肌肉、骨骼、软骨和血管，没有致畸潜力的证据。在心脏毒素肌肉损伤模型中，iMS 细胞对卫星细胞和肌纤维有特殊贡献，而没有异位组织形成。总之，人类脂肪细胞衍生的 iMS 细胞以上下文相关的方式再生组织，而不会出现异位或肿瘤生长。