A low dose of simvastatin enhanced the therapeutic efficacy of mesenchymal stem cell (MSC) transplantation in skin wound healing in diabetic mice associated with increases in pAkt, SDF-1, and angiogenesis

Abstract

PurposeWe aimed to determine the possible mechanisms of underlying the effects of low dose simvastatin on enhancing the therapeutic efficacy of MSC transplantation in diabetic wound healing.\n\nMethodsBalb/c nude mice were divided into five groups:- control mice (CON), diabetic mice (DM), diabetic mice pretreated with low-dose simvastatin (DM+SIM), diabetic mice implanted with MSCs (DM+MSCs) and diabetic mice pretreated with low-dose simvastatin and implanted with MSCs (DM+MSCs+SIM). Seven days before wound induction, low dose simvastatin was orally administered to the DM+SIM and DM+MSCs+SIM groups. Eleven weeks after the induction of diabetes, all mice were given bilateral full-thickness excisional back skin wounds.\n\nResultsBy comparing the DM+MSCs+SIM and DM+MSCs groups, the results showed that on day 14; the wound closure (%WC) and capillary vascularity (%CV) in the DM+MSCs+SIM group were significantly increased compared to those in the DM+MSCs group. In addition, by using immunohistochemical techniques, it was also shown that the expression of SDF-1, a chemotactic factor regulating the migration of stem cells, in the DM+SIM+MSCs group was increased compared with that in the DM+MSCs group. Furthermore, using phospho-Akt (S473) Pan Specific DuoSet IC ELISA (R&D Systems, USA) kits, the increased tissue Akt levels were found in the DM+SIM+MSCs group but not in the other groups.\n\nConclusionsOur study suggests that a low dose of simvastatin enhanced the therapeutic efficacy of MSCs in diabetic wound healing, and this effect was associated with increases in pAkt levels, SDF-1 levels, and angiogenesis, and improved wound closure.