Adipose-derived stem cells promote diabetic wound healing via the recruitment and differentiation of endothelial progenitor cells into endothelial cells mediated by the VEGF-PLCγ-ERK pathway

Adipose-derived stem cell (ADSC) therapy is a promising treatment strategy for wound healing; however, the mechanism underlying this effect remains unclear. In the present study, we aimed to explore the influence of ADSC-derived VEGF on diabetic wounds and its role in modulating endothelial progenitor cells. The effect of ADSCs and ADSC-derived VEGF in vivo was investigated using a diabetic wound healing model, and inflammatory factors, such as IL-6, IL-10, and TNF-alpha, were detected. RT-qPCR and western blot analysis were used to detect the expression of downstream targets. In addition, the role of ADSC-derived VEGF in modulating endothelial progenitor cells (EPCs) was investigated using EdU assay, CD-31 immunofluorescence, and Transwell assay in vitro. The results show that ADSCs accelerated diabetic wound tissue closure and decreased the expression of inflammatory factors, such as IL-6, IL-10, and TNF-alpha. Further molecular mechanism studies indicated that coculturing EPCs with ADSC-conditioned medium enhanced the proliferation, mobilization and differentiation of EPCs into endothelial cells. This enhancement was inhibited when the expression of the VEGF downstream signal molecules VEGFR2, PLC gamma, and ERK1/ERK2 was blocked, indicating that ADSCs might accelerate diabetic wound healing through the recruitment and differentiation of EPCs mediated by VEGF. Overall, the results of the study revealed that ADSCs could promote diabetic wound healing through the recruitment and differentiation of EPCs via angiogenesis effects regulated by the VEGF-PLC gamma-ERK1/ERK2 pathway and suppression of the inflammatory response. In addition, it will be helpful to establish further understanding of ADSC therapy for clinical application.