Comparison between therapeutic effects of low-dose simvastatin and mesenchymal stem cells (MSCs) transplantation on diabetic wound healing
Keywords:
Diabetic wound, simvastatin, mesenchymal stem cells (MSCs)Abstract
Background: Non-healing diabetic ulcers are the most common cause of amputation. Several studies have reported for the therapeutic potency of simvastatin and mesenchymal stem cells (MSCs) on improving angiogenic factors and wound healing.
Objectives: This study is aimed to evaluate and compare the treatment outcomes between low-dose simvastatin and MSCs transplantation in diabetic wound healing.
Methods: Balb/c nude mice were divided into four groups: control group (CON), diabetic wounded group (DM, streptozotocin 45 mg/kg intraperitoneal daily for 5 days), diabetic wounded group with daily oral treatment of simvastatin (DM+SIM) and diabetic wounded group with implanted MSCs (DM+MSCs). Seven days before wound creation, oral simvastatin was started in DM+SIM (0.25mg/kg/day). Eleven weeks after the diabetic induction, all mice were created bilateral full-thickness excisional skin wounds on the back and received fibrin gel or MSCs into wound bed. At day 7 and 14 post wounding, the percentage of wound closure (%WC), the percentage of capillary vascularity (%CV), tissue malondialdehyde (MDA) levels, stromal cell-derived factor 1 (SDF-1) levels, neutrophil infiltration and re-epithelialization were determined by using image analysis, confocal fluorescence microscopy, TBARs assay, immunohistochemically staining and hematoxylin and eosin staining, respectively. Interleukin 6 (IL-6) levels, tissue vascular endothelial growth factor (VEGF) levels, and pAkt levels were determined by using enzyme-linked immunosorbent assay.
Results: The %WC in DM+SIM and DM+MSCs groups were significantly higher when compared to the diabetic group. This study also showed that simvastatin and MSCs could increase %CV, VEGF, pAkt and SDF-1 level. Moreover, tissue MDA, IL-6 and neutrophil infiltration in DM+SIM and DM+MSCs groups were significantly decreased when compared to the diabetic group. Furthermore, the re-epithelialization of DM+MSCs group was significantly increased when compared to the diabetic group.
Conclusion: The results showed no significant difference between groups in all parameters on day 14 post-wound creation. Therefore, low-dose simvastatin might be used as an alternative treatment for diabetic wound healing.
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