Stress-induced senescence in mesenchymal stem cells: Triggers, hallmarks, and current rejuvenation approaches

Mesenchymal stem cells (MSCs) have emerged as promising cell-based therapies in the treatment of degenerative and inflammatory conditions. However, despite accumulating evidence of the breadth of MSC functional potency, their broad clinical translation is hampered by inconsistencies in therapeutic efficacy, which is at least partly due to the phenotypic and functional heterogeneity of MSC populations as they progress towards senescence in vitro. MSC senescence, a natural response to aging and stress, gives rise to altered cellular responses and functional decline. This review describes the key regenerative properties of MSCs; summarises the main triggers, mechanisms, and consequences of MSC senescence; and discusses current cellular and extracellular strategies to delay the onset or progression of senescence, or to rejuvenate biological functions lost to senescence.

Automated summary

Mesenchymal stem cells (MSCs) hold promise as cell-based therapies for degenerative and inflammatory conditions. However, their clinical translation is hindered by the heterogeneity and senescence of MSC populations, leading to inconsistent therapeutic efficacy. This review discusses the regenerative properties of MSCs, the triggers and mechanisms of MSC senescence, and strategies to delay or rejuvenate functions lost to senescence.