Efficacy of extracellular vesicles derived from mesenchymal stromal cells in regulating senescence: <i>In vitro</i> and <i>in vivo</i> insights

BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) can be used for anti-aging therapy and treating various aging-related diseases. However, the clinical application of MSC-EVs is still limited, mainly due to insufficient information on the preparation process, quality, and mechanism of action of MSC-EVs. AIM To study the biological effects of MSC-EVs in regulating cellular senescence. METHODS In this study, we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use. To support the clinical use of our product as a therapeutic agent, we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo . RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associated β-galactosidase, matrix metallopeptidase 1, P21, and interleukin-1β and increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts. Similarly, treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice, aging-related histopathological changes, oxidative stress, and aging-related gene expression. CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism. Overall, these findings strongly suggest that MSC-EVs hold promise for aging therapy.