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.

This study demonstrated that fibroblast derived extracellular vesicle (EV), induced activation of fibroblast, endothelial cell migration, and tube formation in vitro and also induced, in vivo wound healing by enhancing the collagen formation and maturation, increasing Vascular endothelial growth factor (VEGF) expression, blood vessel formation, and skin appendages induction. These findings uncovered; fibroblast derived EV can be used as potential cell free/EV-based candidate for wound healing therapies.
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