Adipose-Derived Stem Cell Exosomes Promote Scar-Free Healing of Diabetic Wounds via miR-204-5p/TGF-β1/Smad Pathway

Numerous researches have demonstrated the therapeutic potential of adipose-derived stem cell exosomes (ADSC-Exos) in promoting wound healing. In this study, we aimed to investigate the impact of ADSC-Exos on diabetic wound fibroblasts and elucidate its possible mechanisms. CCK-8, Edu, cell scratch, and Transwell tests were used to evaluate the function of ADSC-Exos on rat skin fibroblasts (RSFs) in high-glucose (HG) medium. The targeting effect of ADSC-Exo-derived microRNA (miRNA) and TGF-β1 was assessed using bioinformatic analysis and then confirmed with western blot and dual luciferase reporter assays. ADSC-Exos, miR-204-5p mimic, and anti-miR-204-5p mimic were used to stimulate RSFs, and the levels of TGF-β1/Smad pathway were analyzed by western blot. In vivo, digital photo and tissue section staining were used to evaluate the therapeutic effect of ADSC-Exos on diabetic wounds. The data showed that ADSC-Exos enhance the proliferation and migration of fibroblasts under HG conditions, reduce excessive myofibroblast differentiation and collagen deposition, and promote scarless healing of diabetic wounds. Additionally, miR-204-5p in ADSC-Exos targets TGF-β1 to inhibit p-Smad2/3, Col I, and alpha-smooth muscle actin (α-SMA), thereby reducing fibrosis. These findings suggest that ADSC-Exos have potential prospects for promoting diabetic wound healing.