Chulalongkorn Medical Journal


Background: Non-healing diabetic ulcers are the most common cause of amputation. Several studies have reportedfor the therapeutic potency of simvastatin and mesenchymal stem cells (MSCs) on improving angiogenic factorsand wound healing.Objectives: This study is aimed to evaluate and compare the treatment outcomes between low-dose simvastatinand 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 ofsimvastatin (DM+SIM) and diabetic wounded group with implanted MSCs (DM+MSCs). Seven days beforewound 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 MSCsinto wound bed. At day 7 and 14 post wounding, the percentage of wound closure (%WC), the percentage ofcapillary 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 fluorescencemicroscopy, 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 determinedby using enzyme-linked immunosorbent assay.Results: The %WC in DM+SIM and DM+MSCs groups were significantly higher when compared to the diabeticgroup. 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 significantlydecreased when compared to the diabetic group. Furthermore, the re-epithelialization of DM+MSCs group wassignificantly increased when compared to the diabetic group.Conclusion: The results showed no significant difference between groups in all parameters on day 14 post-woundcreation. Therefore, low-dose simvastatin might be used as an alternative treatment for diabetic wound healing.


Faculty of Medicine, Chulalongkorn University

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