Apoptotic bodies extracted from adipose mesenchymal stem cells carry microRNA-21–5p to induce M2 polarization of macrophages and augment skin wound healing by targeting KLF6
School of Medical and Health Sciences / Centre for Precision Health
National Natural Science Foundation of China National Key R&D Program of China Shanghai Shenkang Hospital Development Centre Project
Background: Adipose-derived mesenchymal stem cells (adMSCs) are suggested as potential tools for the treatment of regenerative diseases, including tissue repair. This study aimed to explore the function of adMSC-derived apoptotic bodies in skin wound healing and the molecules of action. Methods: The acquired adMSCs and their-derived apoptotic bodies were identified. A murine model of full-thickness skin wounds was treated with apoptotic bodies. The wound healing process of mice and the pathological changes in wound tissues were examined. Ana-1 macrophages were treated with lipopolysaccharide (LPS) and apoptotic bodies for in vitro experiments. Polarization of macrophages was examined by immunofluorescence staining of the specific biomarkers and ELISA kits. Dermal microvascular endothelial cells (DMECs) or dermal fibroblasts (DFs) were co-cultured with apoptotic bodies or the LPS- and apoptotic bodies-treated Ana-1 cells. Downstream molecules mediated by apoptotic bodies were screened by microarray and bioinformatic analyses. Results: Apoptotic bodies treatment accelerated skin wound healing in mice and promoted formation of granulation tissues and blood vessels in wound tissues. Apoptotic bodies treatment induced M2 polarization of macrophages. The angiogenesis ability of DMECs, and the viability and migration of DFs were increased when co-cultured with the apoptotic bodies-treated Ana-1 cells. MicroRNA (miR)-21–5p was abundantly expressed in ABs, and kruppel like factor 6 (KLF6) mRNA was confirmed as a target of miR-21–5p. Overexpression of KLF6 reduced M2 polarization of macrophages and blocked the promoting effect of apoptotic bodies on wound healing in vitro and in vivo. Conclusion: miR-21–5p carried by adMSC-derived apoptotic bodies targets KLF6 to induce M2 polarization of macrophages and augment skin wound healing.