Mesenchymal stem cells derived EXO-miR3671 delivery promoted angiogenesis and accelerated wound healing of diabetes.

OBJECTIVE

To explore the effect of exosomes-encapsulated miR3671 (EXO-miR3671) from mesenchymal stem cells (MSC) on diabetic wound healing and its mechanism.

METHODS

Bioinformatics analysis was conducted to identify gene and miRNA expression changes associated with diabetic foot ulcer (DFU). A diabetic mouse wound model was established, and dual-luciferase reporter assay was performed to verify the targeting relationship between miR3671 and QSOX1. For in vitro experiments, human umbilical vein endothelial cells (HUVECs) were cultured and transfected; the effects of EXO-miR3671 secreted by mesenchymal stem cells on HUVEC biological functions were detected via EdU proliferation assay, Transwell migration assay, and angiogenesis assay. For in vivo experiments, after dynamic measurement of wound areas in diabetic mice, HE staining, immunohistochemistry, and Western blot were employed to evaluate the regulatory effects of mesenchymal stem cell-derived EXO-miR3671 on wound healing process and related protein expression levels.

RESULTS

MiR3671 was downregulated in DFU tissues and diabetic mouse wounds. EXO-miR3671 promoted HUVEC proliferation, migration, and angiogenesis in vitro. In diabetic mice, it accelerated wound closure, reduced inflammation, increased Ki67+ cell proliferation, and upregulated pro-angiogenic growth factors.

CONCLUSIONS

MSC-derived EXO-miR3671 could be a potential treatment for diabetic wounds, providing new insights for treatment.