Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling

TLDR

Scar formation after skin wounds remains a persistent medical problem, and exosomes derived from human adipose mesenchymal stem cells have been shown to aid wound healing. The study examined whether ASC‑derived exosomes could reduce scar formation and elucidated the underlying mechanisms. Intravenous ASC‑exosomes reduced scar size, shifted collagen III/I and TGF‑β3/TGF‑β1 ratios, inhibited fibroblast‑to‑myofibroblast differentiation, and up‑regulated MMP3 via ERK/MAPK to increase the MMP3/TIMP1 ratio, thereby promoting ECM remodeling and scarless wound repair.

Abstract

Scar formation is an intractable medical problem that appears after skin wounds have healed. Recent research has shown that exosomes secreted by human adipose mesenchymal stem cells (ASC-Exos) can benefit wound healing. To further explore the therapeutic potential of ASC-Exos, we investigated their effects on mitigating scar formation, and the underlying mechanisms of these effects. We found that intravenous injection of ASC-Exos decreased the size of scars and increased the ratio of collagen III to collagen I in murine incisional wounds. Exosome treatment also prevented the differentiation of fibroblasts into myofibroblasts and increased the ratio of transforming growth factor-β3 (TGF-β3) to TGF-β1 in vivo. Additionally, we found that ASC-Exos increased the matrix metalloproteinases-3 (MMP3) expression of skin dermal fibroblasts by activating the ERK/MAPK pathway, leading to a high ratio of MMP3 to tissue inhibitor of matrix metalloproteinases-1 (TIMP1), which is also beneficial for the remodelling of extracellular matrix (ECM). In conclusion, our results demonstrated that ASC-Exos promote ECM reconstruction in cutaneous wound repair by regulating the ratios of collagen type III: type I, TGF-β3:TGF-β1 and MMP3:TIMP1, and by regulating fibroblast differentiation to mitigate scar formation. Therefore, the application of ASC-Exos may be a novel therapeutic approach for scarless wound repair.