Human fibroblast-derived extracellular vesicles promote hair growth in cultured human hair follicles

Hair loss is a prevalent medical condition affecting both genders. In this study, we investigate the effects of a specific class of extracellular vesicles (EVs), namely human normal fibroblast-derived EVs (hFB-EVs), on human dermal papilla (DP) and outer root sheath (ORS) cells and examine the molecular mechanisms responsible for hair growth in hair follicles (HFs). We find that Wnt3a, which maintains the hair-generating activity of DP cells, is enriched and more strongly associated with hFB-EVs than with fibroblasts. Furthermore, hFB-EV-associated Wnt3a mediated receptor activation in cultured DP cells, leading to an increase in beta-catenin in the cytoplasm and its translocation into the nucleus, thereby elevating expression of the target genes Axin2 and Lef1. Additionally, hFB-EVs promoted the migration, proliferation, and differentiation of ORS cells and elongation of the hair shaft in human HFs. These findings revealed a novel mechanism by which hFB-EVs influence hair growth.