Adipose‐Derived Stem Cell Exosomes Promote Scar‐Free Healing of Diabetic Wounds via miR‐204‐5p/TGF‐ <i>β</i> 1/Smad Pathway
Peijun Song, Qiu Liang, Xiuyu Ge, D. Zhou, Mei Yuan, Weiwei Chu, Jing Xu
Abstract
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‐ β 1 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‐ β 1/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‐ β 1 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.