Exosome-carried miR-1248 from adipose-derived stem cells improves angiogenesis in diabetes-associated wounds

Chronic non-healing wounds are a common complication of diabetes, marked by impaired angiogenesis. This study explores how exosomes (Exo-miR-1248) from miR-1248-overexpressing adipose-derived stem cells enhance diabetic wound healing by modulating endothelial cell function. Adipose-derived stem cells were transfected with a lentivirus carrying miR-1248 to produce Exo-miR-1248, isolated via differential centrifugation. In vitro, Exo-miR-1248's effects on proliferation, scratch wound healing, and tube formation in human umbilical vein endothelial cells (HUVECs) were assessed. For in vivo analysis, diabetic mice were induced with streptozotocin (STZ) and full-thickness skin defects were created. The impact of Exo-miR-1248 on wound healing was evaluated through subcutaneous injections. Histological analysis included H&E staining for epithelial regeneration and wound width, Masson's staining for collagen deposition, immunofluorescence for CD31 and α-SMA expression, RT-qPCR and WB for mRNA and protein levels of pro-angiogenic genes (VEGF-A, TGF-β, and Angpt-1). Exo-miR-1248 significantly enhanced HUVEC proliferation and migration. Tube formation assays showed increased capillary-like structures. In vivo, Exo-miR-1248-treated wounds healed faster, with improved collagen deposition and blood vessel formation. RT-qPCR and WB show that the mRNA and protein levels of VEGF-A, Angpt-1, and TGF-β are upregulated. Exo-miR-1248 may enhance diabetic wound healing by upregulating pro-angiogenic factors, offering a novel therapeutic approach.