Although human adipose derived stem cells (hADSCs) hold great promises for regenerative medicine, their key biological properties remain poorly understood. In particular, proliferation defects resulted from deep quiescence (dormancy) and senescence represent a major hurdle in hADSC production and clinical application. We have developed a model system for mechanistic dissection of hADSC quiescence and senescence. p57^Kip2, a major CDK inhibitor, was highly expressed in quiescent and senescent hADSCs but its level quickly declined upon stem cell activation. p57^Kip2 overexpression induced quiescence in spite of proliferative signals and its knockdown promoted cell cycle reentry even with induction of quiescence presumably through modulating the CDK2–CyclinE1 complex. Given its key role in quiescence and senescence, p57^Kip2 may be exploited for innovative strategies to amplify hADSCs of high quality for clinics.

尽管人类脂肪干细胞（hADSCs）在再生医学方面具有广阔的前景，但其关键生物学特性仍然知之甚少。特别是，深层静止（休眠）和衰老导致的增殖缺陷是hADSC生产和临床应用的主要障碍。我们已经开发了用于hADSC静息和衰老的机械解剖的模型系统。p57 ^Kip2，一种主要的CDK抑制剂，在静止和衰老的hADSCs中高度表达，但其水平在干细胞激活后迅速下降。p57 ^Kip2尽管有增生信号，但过表达诱导的静止，其敲低促进了细胞周期的再进入，即使推测是通过调节CDK2-CyclinE1复合物也引起了静止。鉴于其在静止和衰老中的关键作用，p57 ^Kip2可能被用于创新策略以扩增临床高质量的^hADSC。