Human Umbilical Cord Blood Plasma-Derived Exosomal miR-410-3p Alleviates Liver Injury by Regulating the Mitochondria-Mediated Antiapoptotic Signaling

Abstract

Severe liver injury is a life-threatening condition with high mortality and limited therapeutic options. Extensive research on heterochronic parabiosis has highlighted the potent regenerative repair capabilities of young blood in tissue regeneration. However, it remains unclear whether younger blood, specifically umbilical cord blood, can offer similar benefits for tissue repair. In this study, we demonstrate that exosomes derived from umbilical cord blood plasma (CBP-Exos) exhibit significant therapeutic effects in both acute and chronic liver injury models, outperforming exosomes from young peripheral blood plasma. Treatment with CBP-Exos notably reduced liver necrosis, lipid peroxidation, and apoptosis in liver tissues of acute liver injury (ALI) mice. Mechanistically, miR-410-3p, derived from CBP-Exos, directly targets the proapoptotic gene Bim for posttranscriptional degradation. The downregulation of Bim facilitates the activation of mitochondrial-mediated Bcl2-CytoC antiapoptotic signaling, resulting in the restoration of mitochondrial structure and function, thereby inhibiting hepatocyte apoptosis and oxidative stress. Furthermore, overexpression of miR-410-3p significantly improved liver function in ALI mice. These findings identify the therapeutic effects of CBP-Exos are attributed to the miR-410-3p/Bcl2/CytoC axis, laying a foundation for the clinical application of CBP-Exos and miR-410-3p in liver diseases.