Exosomes Derived from Epidermal Stem Cells Diabetic Wound

Diabetic foot ulceration is a major diabetic complication with unmet needs. We investigated the efficacy of epidermal stem cells and epidermal stem cells-derived exosomes (ESCs-Exo) in improving impaired diabetic wound healing and their mechanisms of action. In vitro experiments showed that ESCs-Exo enhanced the proliferation and migration of diabetic fibroblasts and macrophages and promoted alternative or M2 macro-phage polarization. In wounds of db/db mice, treatment with both epidermal stem cells and ESCs-Exo, when compared with fibroblast exosomes and PBS control, accelerated wound healing by decreasing inflammation, augmenting wound cell proliferation, stimulating angiogenesis, and inducing M2 macrophage polarization. Multiplex protein quantification of wound lysates revealed TGFf3 signaling influenced by ESCs-Exo. High -throughput sequencing of small RNAs contained in the ESCs-Exo showed higher proportions of microRNAs than those contained in fibroblast exosomes. In silico functional analysis showed that the ESCs-Exo micro-RNAs-target genes were primarily involved in homeostatic processes and cell differentiation and highlighted regulatory control of phosphatidylinositol-3 kinase/protein kinase B and TGFf3 signaling pathways. This was also validated in vitro. Collectively, our results indicate that epidermal stem cells and ESCs-Exo are equally effective in promoting impaired diabetic wound healing and that ESCs-Exo treatment may be a promising and technically advantageous alternative to stem cell therapies.

Automated summary

This study investigated the efficacy and mechanisms of epidermal stem cells and their derived exosomes in improving diabetic foot ulceration. The results showed that both epidermal stem cells and their exosomes were effective in promoting diabetic wound healing, and exosome treatment may be a promising alternative to stem cell therapies.