Abstract
BackgroundDiabetic 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.MethodsAlbino 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.ResultsOur 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.ConclusionsThese data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
Highlights
Diabetes mellitus (DM) is a worldwide health problem affecting approximately 9.3% of the global population with its prevalence expected to rise by 25% in 2030 and 51% in 2045 [1]
Ebrahim et al Stem Cell Research & Therapy (2021) 12:392. These data demonstrated that platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells (ADSCs) combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and epidermal stem cells (EPSCs) proliferation
The epidermal stem cells (EPSC) are a type of autologous adult stem cells that exist in the epidermis and the hair follicles ensuring the preservation of adult skin hemostasis and hair regeneration; EPSC participates in the repair of the injured epidermis [3]
Summary
Diabetes mellitus (DM) is a worldwide health problem affecting approximately 9.3% of the global population with its prevalence expected to rise by 25% in 2030 and 51% in 2045 [1]. The healing progression may be disrupted, developing scar tissue devoid of the hair follicle and sweat glands [4]. This indicates that the process of wound healing is associated with interaction among cells, complex regulation of the extracellular matrix, and various paracrine elements [5]. 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. 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
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