Wharton’s jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat

Abstract

Background Diabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton’s jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored. Methods Firstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay. Results In diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo. Conclusion PF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.

Decellularized Wharton’s Jelly: Biomaterial Potential for Regenerative Medicine Applications - A Mini-Review

“…In the same manner, Hashemi and coauthors 2019 in observed that (WJSCs) seeded on an amniotic membrane could promote a healing effect in diabetic wounds [24]. The application of WJ-MSCs enclosed with PF-127/SAP also promoted cell proliferation, neovascularization, and wound diabetic healing in rats [25].…”

Transplantation of Wharton's jelly mesenchymal stem cells encapsulated with Hydroactive® Gel promotes diabetic wound antifibrotic healing in type 2 diabetic rats

“…The diabetic rat model was conducted as per our previous study report. 27 Sprague Dawley (SD) rats were housed at a constant temperature and humidity. High-glucose and high-fat diets were used to feed the SD rats for 4 weeks.…”

“…26 Our previous study demonstrated that PF-127 plus 400 μM sodium ascorbyl phosphate (SAP) can prolong the retention time of WJMSCs and promote diabetic wound healing and regeneration. 27 Although PF-127/SAP system could deliver WJMSCs to the wound site effectively, however, the survival and viability of WJMSCs embedded in the PF-127/SAP combination were still low. Hydroactive gel is a sterile transparent gel made of natural hydrocolloid composed of pectin and sodium carboxymethyl cellulose that has been widely used for the management of partial- and full-thickness wounds.…”

Current Advances in the Development of Hydrogel-Based Wound Dressings for Diabetic Foot Ulcer Treatment

“…Within this family of polymers, Pluronic F-127 hydrogels have increasingly drawn attention, as they can be safely used as synthetic platforms for the delivery of drugs and cells through in situ gelation at body temperature [ 109 , 110 , 111 ]. For instance, Jiao et al recently evaluated the effect of Wharton’s jelly mesenchymal stem cells (WJMSCs) encapsulated in a Pluronic F-127 hydrogel (20% w / v ) on the healing process of a type 2 diabetes wound model [ 89 ]. Prior to encapsulation, the hydrogel precursor was supplemented with sodium ascorbyl phosphate to increase WJMSC viability.…”