Exosomal miR-17–92 derived from human mesenchymal stem cells promotes wound healing by enhancing angiogenesis and inhibiting endothelial cell ferroptosis

Wound healing is a complex and dynamic process that involves a series of cellular and molecular events. Mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have crucial functions in cutaneous wound healing. MiR-17-92 is a multifunctional microRNA (miRNA) cluster that plays vital roles in tissue development and tumor angiogenesis. This study aimed to explore the function of miR-17.92 in wound healing as a component of MSC-Exos.Human MSCs were cultured in serum-free medium, and exosomes were collected by ultracentrifugation. The levels of miR-17-92 in MSCs and MSC-Exos were determined by quantitative real-time polymerase chain reaction. MSC-Exos were topically applied to full-thickness excision wounds in the skin of miR-17-92 knockout (KO) and wild-type (WT) mice. The proangiogenic and antiferroptotic effects of MSC-Exos overexpressing miR-17-92 were assayed by evaluating the relative levels of angiogenic and ferroptotic markers.MiRNA-17-92 was found to be highly expressed in MSCs and enriched in MSC-Exos. Moreover, MSC-Exos promoted the proliferation and migration of human umbilical vein endothelial cells in vitro. KO of miR-17-92 effectively attenuated the promotion of wound healing by MSC-Exos. Furthermore, exosomes derived from miR-17-92-overexpressing human umbilical cord-derived MSCs accelerated cell proliferation, migration, angiogenesis, and enhanced against erastin-induced ferroptosis in vitro. miR-17-92 plays a key role in the protective effects of MSC-Exos against erastin-induced ferroptosis in HUVECs CONCLUSION: These findings suggest that miR-17-92 participates in the repair ability of MSC-Exos and that miR-17-92-overexpressing exosomes may represent a new strategy for cutaneous wound repair.