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微环境调控间充质干细胞复制性衰老的研究进展

郭旬会^1,2, 魏文娟¹, 关心¹, 邹伟^2,3, 刘晶^1,2,3,*

¹大连医科大学附属第一医院干细胞临床研究机构，大连 116011；²大连干细胞与精准医学创新研究院，大连 116023；³辽宁省干细胞与精准医学前沿技术重点实验室，大连 116023

摘要

间充质干细胞(mesenchymal stem cells, MSCs)是一类能自我更新和分化的多能细胞。越来越多的证据表明，MSCs在再生医学和组织工程等领域具有重要的作用。但是值得注意的是，与很多细胞一样，MSCs在长期体外扩增过程中会逐渐衰老，出现迁徙能力减弱、增殖速度减慢和分化潜能下降等干性减退的现象，这极大地阻碍了MSCs的应用。目前公认的引起MSCs复制性衰老的因素之一就是细胞生长的微环境。新近研究显示，外源性给药、氧浓度调节、细胞外基质(extracellular matrix, ECM)构建等最新技术都可以通过模拟或者调控微环境来改善干细胞的行为，延缓干细胞复制性衰老。本文首先综述了近年来关于MSCs复制性衰老特征和分子机制方面的研究进展，然后总结了通过改变微环境来保持MSCs干性的技术和方法，旨在为未来MSCs制剂大规模应用于组织工程和临床研究提供参考。

关键词： 间充质干细胞; 复制性衰老; 微环境

Progress in replicative senescence of mesenchymal stem cells regulated by microenvironment

GUO Xun-Hui^1,2, WEI Wen-Juan¹, GUAN Xin¹, ZOU Wei^2,3, LIU Jing^1,2,3,*

¹Clinical Research Institute of Stem Cells, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China；²Dalian Institute of Stem Cell and Precision Medicine Innovation, Dalian 116023, China；³Liaoning Key Laboratory of Stem Cell and Precision Medicine, Dalian 116023, China

Abstract

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.

Key words: mesenchymal stem cells; replicative senescence; microenvironment

收稿日期：　　录用日期：

通讯作者：刘晶　　E-mail: liujing.dlrmc@hotmail.com

DOI: 10.13294/j.aps.2022.0050

引用本文：

郭旬会, 魏文娟, 关心, 邹伟, 刘晶. 微环境调控间充质干细胞复制性衰老的研究进展[J]. 生理学报 2022; 74 (3): 469-478.

GUO Xun-Hui, WEI Wen-Juan, GUAN Xin, ZOU Wei, LIU Jing. Progress in replicative senescence of mesenchymal stem cells regulated by microenvironment. Acta Physiol Sin 2022; 74 (3): 469-478 (in Chinese with English abstract).