Exosomes from adipose derived stem cells improve perforator flap survival through miR-590-3p-mediated M2 macrophage polarization and angiogenesis function

Background : Adipose-derived stem cell exosomes (ADSCs-Exos) are crucial in macrophage polarization and offer therapeutic potential for enhancing wound healing in perforator flaps. However, the mechanisms through which ADSCs-Exos facilitate wound healing and angiogenesis in these flaps are not fully understood. This study aims to elucidate the role of ADSCs-Exos in modulating macrophage activity and promoting vascularization and tissue repair in perforator flaps. Methods :We successfully isolated and confirmed ADSCs exosomes and assessed their effects on macrophage polarization and miR-590-3p expression by co-culturing ADSC-Exos with macrophages.We manipulated the expression of the target gene (miR-590-3p or STAT1) in macrophages to investigate its impact on macrophage polarization. The effects of upregulating or downregulating target genes on endothelial cell proliferation, migration, and angiogenesis were evaluated by co-culturing macrophages with endothelial cells. By applying the supernatant of macrophages with either overexpression or knockdown of the target gene to the SD rat perforator flap model, we investigated the effects of miR-590-3p/STAT1 pathway-mediated macrophage polarization on inflammation and angiogenesis of the perforator flap, and explored the underlying mechanism. Results : We found that miR-590-3p was highly expressed in ADSCs-Exos and promoted M2 macrophage polarization through STAT1, reducing the expression of TNF-αand NOS2 and promoting the expression of Arg-1.By altering the expression of miR-590-3p and STAT1 in macrophages, the study demonstrated enhanced endothelial cell proliferation, migration, and angiogenesis. In a rat perforator flap model, the application of macrophage supernatant with overexpressed or knocked-down target genes showed that ADSC-Exos, mediated by the miR-590-3p/STAT1 pathway, reduced inflammation, improved Choke II vessels, and promoted wound healing. Conclusions: The study identifies a novel therapeutic mechanism where miR-590-3p in ADSC exosomes regulates the miR-590-3p/STAT1 pathway, leading to reduced inflammation, improved vascularization in perforator flaps, and enhanced wound healing. These findings suggest that ADSCs-Exos could be a promising approach for treating complex wounds, offering new avenues for therapeutic interventions aimed at improving vascularization and tissue repair.