Optogenetic Engineered Umbilical Cord MSCs-derived Exosomes For Remodeling Of The Immune Microenvironment In Diabetic Wounds And Promoting Tissue Repair

Angiogenesis and tissue repair in diabetic chronic wounds remains a critical clinical problem.While,engineered MSC-derived exosomes have great potential to promote wound healing.In this study,we discuss the effects and mechanisms of e NOS-rich umbilical cord MSC exosomes(UCMSC-exo/e NOS)modified by genetic engineering and optogenetic techniques on diabetic chronic wound repair.Umbilical cord MSCs expressing two recombinant proteins,CIBN-EGFP-CD9 and e NOS-m Cherry-CRY2,were constructed by genetic engineering.e NOS can be substantially enriched in UCMSCs-exo by endogenous cellular activities under blue light irradiation,and UCMSC-exo/e NOS was purified by ultracentrifugation.In vitro,UCMSC-exo/e NOS significantly promoted the proliferation and migration ability of fibroblasts and vascular endothelial cells inhibited by high glucose.Also,UCMSC-exo/e NOS reduced the expression of inflammatory factors and apoptosis induced by oxidative stress.In vivo,UCMSC-exo/e NOS significantly promoted the rate of wound closure and improved vascular neogenesis and matrix remodeling in diabetic mice.UCMSC-exo/e NOS activated multiple phosphorylation cascade signaling pathways and signaling molecules.UCMSC-exo/e NOS improved the inflammatory profile of the wound site and modulated the associated immune microenvironment,exerting a powerful of tissue repair.This study provides a novel therapeutic strategy based on engineered stem cell-derived exosomes for angiogenesis and tissue repair in diabetic chronic wounds.