Semaphorin7A-expressing mast cell exosomes promote wound healing

Emerging evidence indicates that mast cells contribute to tissue repair, in addition to their well-established roles in immunity. We previously showed the effects of conditioned medium derived from the human mast cell line HMC-1 on skin wound healing. In this study, we assessed the regenerative potential of HMC-1 exosomes in the skin wound healing process and identified the key molecules involved. HMC-1 exosomes are rich in semaphorin 7A (SEMA7A), a key regulator of extracellular matrix (ECM) remodeling, along with canonical exosomal markers. We found that HMC-1 exosomes could promote dermal fibroblast proliferation and upregulate fibronectin and collagen type I expression. Furthermore, topical application of HMC-1 exosomes accelerated wound closure and enhanced tissue regeneration in both wild-type and mast cell-deficient mice. Notably, SEMA7A-deficient HMC-1 exosomes exhibited reduced ECM synthesis in dermal fibroblasts and impaired wound healing in vivo, regardless of the presence of mast cells. These findings suggest that mast cell-derived exosomes can serve as promising cell-free therapeutic agents for wound repair.