Background: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high
disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due
to its high content of growth factors. However, its application is limited due to the rapid degradation of growth
factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells
(ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway.
Methods: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic),
diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined
therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis.
Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like
canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic
marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs)
related gene (ß1 Integrin) were assessed.
Results: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14
days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in
area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly
downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and
diabetic groups.