Extracellular vesicles derived from embryonic day 13 fetal mouse dermal fibroblasts exhibit potential antifibrotic activity

Mice exhibit complete scarless wound healing, including restoration of skin texture, until embryonic day 13 (E13), whereas wounds created on or after embryonic day 17 (E17) result in scar formation. Regeneration is thought to depend on dermal fibroblasts at E13, whereas fascia fibroblasts at E17 contribute to scar formation. Therefore, we examined whether extracellular vesicles (EVs) could be isolated from E13 dermis and whether these EVs could be utilized as an anti-scarring therapy. The addition of EVs derived from E13 dermal fibroblasts (E13D EVs) exerted antifibrotic effects on transforming growth factor-β1 (TGF-β1)-stimulated E17 fascia fibroblasts. E13D EVs also suppressed the fibrotic phenotype of human keloid-derived fibroblasts. In contrast, EVs derived from E17 fascia fibroblasts (E17F EVs), adult mouse fascia fibroblasts (AdF EVs), and human keloid fibroblasts (keloid EVs) enhanced fibrotic responses. These findings suggest that E13 dermal fibroblasts possess intrinsic antifibrotic properties and that these factors may be functionally transferred via EVs. Further characterization of the microRNAs (miRNAs) and proteins contained in E13D EVs may lead to the development of new therapeutic strategies for human scar management and fibrotic skin diseases.