Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions

Abstract Extracellular vesicles (EVs) have been exhibited as promising candidates for delivering endogenous therapeutic cargos for regenerative therapies. Fibroblasts could be candidate source cells for EVs, to investigate their therapeutic effects in wound healing. Here we demonstrated the isolation and characterization of fibroblast-derived (L929 cell line) EVs (L929-EVs). Furthermore, L929-EVs treatment showed pro-wound healing effects in vitro by enhancing proliferation, migration, and scarless wound healing related genes in fibroblast cells. L929-EVs treatment also enhanced the migration and tube formation of endothelial cells. The combination of L929-EVs with fibrin glue accelerated wound healing in the mouse skin wound model by enhancing collagen formation, collagen maturation, and blood vessels in the wounded skin. The role of fibroblast-derived EVs in wound healing could be an important phenomenon, and fibroblast-derived EVs could be harnessed for wound healing therapies.