Zhou Xueke, Hong Yimei, Zhang Hao, Li Xin
Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
School of Medicine, South China University of Technology, Guangzhou, China.
Front Cell Dev Biol. 2020 Jun 3;8:364. doi: 10.3389/fcell.2020.00364. eCollection 2020.
Over the past decades, mesenchymal stem cell (MSC)-based therapy has been intensively investigated and shown promising results in the treatment of various diseases due to their easy isolation, multiple lineage differentiation potential and immunomodulatory effects. To date, hundreds of phase I and II clinical trials using MSCs have been completed and many are ongoing. Accumulating evidence has shown that transplanted allogeneic MSCs lose their beneficial effects due to immunorejection. Nevertheless, the function of autologous MSCs is adversely affected by age, a process termed senescence, thus limiting their therapeutic potential. Despite great advances in knowledge, the potential mechanisms underlying MSC senescence are not entirely clear. Understanding the molecular mechanisms that contribute to MSC senescence is crucial when exploring novel strategies to rejuvenate senescent MSCs. In this review, we aim to provide an overview of the biological features of senescent MSCs and the recent progress made regarding the underlying mechanisms including epigenetic changes, autophagy, mitochondrial dysfunction and telomere shortening. We also summarize the current approaches to rejuvenate senescent MSCs including gene modification and pretreatment strategies. Collectively, rejuvenation of senescent MSCs is a promising strategy to enhance the efficacy of autologous MSC-based therapy, especially in elderly patients.
在过去几十年中，基于间充质干细胞（MSC）的疗法得到了深入研究，并因其易于分离、多向分化潜能和免疫调节作用，在各种疾病的治疗中显示出了有前景的结果。迄今为止，数百项使用MSC的I期和II期临床试验已经完成，许多试验仍在进行中。越来越多的证据表明，由于免疫排斥，移植的异体MSC会失去其有益作用。然而，自体MSC的功能会受到衰老（一个称为衰老的过程）的不利影响，从而限制了它们的治疗潜力。尽管在这方面有了很大进展，但MSC衰老的潜在机制仍不完全清楚。在探索使衰老的MSC恢复活力的新策略时，了解导致MSC衰老的分子机制至关重要。在这篇综述中，我们旨在概述衰老的MSC的生物学特征以及在潜在机制方面取得的最新进展，包括表观遗传变化、自噬、线粒体功能障碍和端粒缩短。我们还总结了目前使衰老的MSC恢复活力的方法，包括基因修饰和预处理策略。总的来说，使衰老的MSC恢复活力是一种有前景的策略，可以提高基于自体MSC疗法的疗效，特别是在老年患者中。
