Engineered BMSCs-Derived Exosomal miR-542-3p Promotes Cutaneous Wound Healing

• Published in: Endocrine, metabolic & immune disorders drug targets Vol. 23; no. 3; p. 336
• Main Authors: Xiong, Qing-Hua, Zhao, Lei, Wan, Guan-Qun, Hu, Yun-Gang, Li, Xiao-Lin
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2023
• Subjects: Animals; Collagen; Disease Models, Animal; Endothelial Cells - metabolism; Humans; Mesenchymal Stem Cells - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Wound Healing - genetics; miRNA-542-3p; wound healing; HMECs; NTA; Bone marrow mesenchymal stem cells (BMSCs); exosomes
• ISSN: 2212-3873
• DOI: 10.2174/1871530322666220523151713

The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCsderived Exosomal miR-542-3p in skin wound mouse models. Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo was loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model. MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure. This study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.