Graphene oxide promotes diabetic skin wound healing through regulating adipose-derived mesenchymal stem cells / 中华内分泌代谢杂志

ABSTRACT

Objective:To study the effect of graphene oxide (GO) on adipose-derived mesenchymal stem cells (Ad-MSCs) to promote diabetic skin wound healing.Methods:Ad-MSCs were cultured with GO at concentration of 100, 200, and 400 μg/mL and with 25 mmol/L of glucose for 48 h. The apoptosis of Ad-MSCs was detected by flow cytometry and Western blotting. Eighteen BALB/c thymus free female nude mice were selected to establish the skin defect model of diabetic nude mice. Then phosphate-buffered saline, Ad-MSCs, and GO+ Ad-MSCs were injected into the damaged skin of nude mice by intradermal injection for treatment, thereby created the control group, Ad-MSCs group, and GO+ Ad-MSCs group, 6 mice each group. The survival of wound cells and skin healing of mice were observed after surgery, and the wound healing was determined by HE staining and Masson staining.The level of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA).Results:Compared with the high glucose group without GO(control group), the apoptosis rate of Ad-MSCs co-culture with GO was significantly reduced( P<0.05), and the apoptosis rate decreased with the increase of GO concentration. The expression level of Bax protein decreased, and the expression level of Bcl-2 protein increased ( P<0.05). Diabetic skin defect model showed that the survival rate of Ad-MSCs and wound healing degree in GO+ Ad-MSCs group were significantly increased ( P<0.05), and the degree of epithelialization and thickness of collagen regeneration were better than those in other groups. ELISA results showed that the expressions of EGF and VEGF were significantly increased in GO+ Ad-MSCs group ( P<0.05), while the expressions of TNF-α and IL-6 were significantly decreased ( P<0.05). Conclusion:GO can inhibit the apoptosis of Ad-MSCs in vitro. In vivo, Ad-MSCs treated with GO have higher survival rate, faster wound healing, and better effect than Ad-MSCs treated alone.