自噬与间充质干细胞衰老的关系研究进展

Research Progress on the Relationship Between Autophagy and Mesenchymal Stem Cell Senescence

间充质干细胞(mesenchymal stem cells,MSCs)具备多向分化、免疫调控和靶向迁移的能力,在再生医学领域一直备受关注。但是,随着供体年龄的增长和体外培养时间的延长,MSCs通常表现出衰老特征。MSCs衰老以及功能衰退被认为是机体衰老和相关退行性疾病发展的重要诱发因素,同时也制约着MSCs在再生医学领域中的应用。自噬是溶酶体依赖途径介导细胞内物质的降解和再循环过程,是真核细胞的非核(细胞质)部分得以更新的有效途径,对维持细胞稳态至关重要,是调节MSCs衰老的潜在调控靶标。对MSCs衰老的表型特征、功能变化和分子机制,以及自噬与衰老之间的关系进行综述,为促进MSCs临床应用提供理论基础。

Mesenchymal stem cells(MSCs)have attracted great attention in regenerative medicine due to their capacities for multilineage differentiation,immunomodulation and migration.However,increased donor age and prolonged in vitro culture inevitably trigger senescence.MSC senescence and cellular dysfunction are considered one of the main causes of aging in an individual and the development of degenerative diseases,while they hinder the application of MSCs in regenerative medicine.As a major lysosome-dependent degradation and recycling pathway,autophagy is the mechanism through which the cytoplasmic components can be renewed,contributing to maintaining intracellular homeostasis and resisting environmental stress,and may become a potential therapeutic target for regulating MSC secescence.This review focuses on the phenotypic characterizations,functional alterations and molecular mechanisms in senescent MSCs,and the relationship between autophagy and senescence,which develop a theoretical foundation for the research and clinical application of MSCs.