Endothelial progenitor cell derived extracellular vesicles promotes wound healing in diabetic mice via activating mobilization and neovascularization

Diabetic patients face delayed wound healing due to angiogenesis dysfunction. This study aims to investigate the function of endothelial progenitor cell (EPC)-derived extracellular vesicles (EVs) in wound healing of diabetic mice, providing a theoretical basis for treating difficult-to-heal diabetic wounds. The full-thickness skin wound model was used as an animal model. After treatment with EPC-EVs, wound healing and histopathological structures were evaluated. Peripheral blood was collected to analyze circulating EPCs. In cell models, EV endocytosis, cell viability, angiogenic capacity, and cell migration were detected. miR-204-5p, lncRNA SNHG1, EIF4A3, and HDAC6 were detected. EVs derived from EPCs with miR-204-5p overexpression were extracted to investigate their effects on wound healing. The bindings between miR-204-5p and SNHG1, SNHG1 and EIF4A3, and EIF4A3 and HDAC6 mRNA were validated. EPC-EVs promoted wound healing in diabetic mice. EPC-EVs enhanced angiogenesis and migration in cell models. EPC-EVs with miR-204-5p overexpression exhibited better therapeutic effects. EPC-EVs delivered miR-204-5p into tissues/cells to lower SNHG1 expression. SNHG1 bound to EIF4A3 to increase HDAC6 expression. SNHG1/HDAC6 overexpression partly reversed the pro-angiogenic effects of EPC-EVs on diabetic wound healing and HG-impaired endothelial cells. In conclusion, EPC-EVs enhance EPC mobilization and angiogenesis to accelerate wound repair in diabetic mice via the miR-204-5p/SNHG1/HDAC6 axis.