Adipose-mesenchymal stem cell-derived extracellular vesicles enhance angiogenesis and skin wound healing via bFGF-mediated VEGF expression.

Abstract

This study aimed to investigate whether extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ASCs) promote skin wound healing by delivering basic fibroblast growth factor (bFGF) to enhance vascular endothelial growth factor (VEGF) expression. ASCs were isolated and transfected with either a bFGF knockdown lentivirus (Lv-sh-bFGF) or a control lentivirus (Lv-sh-NC). EVs were extracted from ASCs cultures and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting for surface markers. EVs were extracted from the conditioned mediums of ASCs and subjected to different treatments. These EVs or control treatments were injected at the wound edges. Wound healing was assessed using histological techniques, including H&E and Masson's trichrome staining to evaluate tissue regeneration, collagen organization, and immunohistochemistry for CD31 to quantify microvessel density. Protein expression of bFGF and VEGF was measured by Western blotting. ASC-derived EVs significantly promoted angiogenesis and improved skin wound healing. EVs encapsulating bFGF enhanced VEGF expression in the wound tissue, while knockdown of bFGF reduced both bFGF and VEGF expression, leading to delayed wound healing. Further knockdown of VEGF partially reversed the pro-angiogenic and wound-healing effects of bFGF-encapsulated EVs. This study demonstrates that ASC-derived EVs promoted skin wound repair by enhancing angiogenesis and accelerating tissue regeneration through the bFGF/VEGF axis. These findings highlight the therapeutic potential of ASCs-derived EVs in improving skin wound healing.