Mesenchymal Stem Cell-Mediated Vascular Regeneration in Diabetic Foot Ulcers via the Notch Signaling Pathway.

OBJECTIVE: Diabetic Foot Ulcers (DFUs) represent a prevalent and serious complication of diabetes, frequently resulting in persistent wounds and delayed healing. This research explores the healing effects of mesenchymal stem cells (MSCs) on DFUs and examines the involvement of Notch signaling in this therapeutic process. METHODS: BALB/c mice were induced with diabetes using streptozotocin (STZ) and divided into five groups: Control, Model, MSCs Treatment, MSCs + Notch Inhibition, and MSCs + Notch Activation. Wound healing was monitored, and tissue samples were analyzed using histological and molecular techniques. RESULTS: Our results demonstrated that MSCs treatment significantly accelerated wound healing, as evidenced by improved histopathology and enhanced expression of CD31, VEGF, FGF, and PECAM-1 in MSCs-treated groups. Notch activation further enhanced MSCs-mediated healing, as shown by increased Notch1 and Jagged-1 protein levels. Conversely, the MSCs + Notch Inhibition Group showed reduced healing and similar results to the Model Group, with lower expression of Notch1 and Jagged-1. CONCLUSION: These findings suggest that MSCs promote DFU healing, and Notch signaling plays a crucial role in enhancing MSC-mediated repair. Our results highlight the potential of MSC-based therapies combined with Notch pathway modulation as a promising strategy for improving DFU treatment and wound healing in diabetic patients.