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Augmentation of neovascularization in murine hindlimb ischemia by combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells transplantation

We postulated that combining high-dose simvastatin with bone marrow derived-mesenchymal stem cells (MSCs) delivery may give better prognosis in a mouse hindlimb ischemia model. Methods: Mouse hindlimb ischemia model was established by ligating the right femoral artery. Animals were grouped (n = 10) to receive local injection of saline without cells (control and simvastatin groups) or with 5 × 106 MSCs (MSCs group).Animals received either simvastatin (20 mg/kg/d, simvastatin and combination groups) or saline (control and MSCs group) gavages for continual 21 days. The blood flow was assessed by laser Doppler. | Li et al. Journal of Biomedical Science 2010 17 75 http www.jbiomedsci.eom content 17 1 75 tì.NSC The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Augmentation of neovascularization in murine hindlimb ischemia by combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells transplantation Yong Li1 2t Dingguo Zhang3t Yuqing Zhang4t Guoping He2 Fumin Zhang1 Abstract Objectives We postulated that combining high-dose simvastatin with bone marrow derived-mesenchymal stem cells MSCs delivery may give better prognosis in a mouse hindlimb ischemia model. Methods Mouse hindlimb ischemia model was established by ligating the right femoral artery. Animals were grouped n 10 to receive local injection of saline without cells control and simvastatin groups or with 5 X 106 MSCs MSCs group .Animals received either simvastatin 20 mg kg d simvastatin and combination groups or saline control and MSCs group gavages for continual 21 days. The blood flow was assessed by laser Doppler imaging at day 0 10 and 21 after surgery respectively. Ischemic muscle was harvested for immunohistological assessments and for VEGF protein detection using western blot assay at 21 days post-surgery. In vitro MSCs viability was measured by MTT and flow cytometry following culture in serum-free medium for 24 h with or without simvastatin. Release of VEGF by MSCs incubated with different doses of simvastatin was assayed using ELISA. Results Combined treatment with simvastatin and MSCs induced a significant improvement in blood reperfusion a notable increase in capillary density a highest level of VEGF protein and a significant decrease in muscle cell apoptosis compared with other groups. In vitro simvastatin inhibited MSCs apoptosis and increased VEGF release by MSCs. Conclusions Combination therapy with high-dose simvastatin and bone marrow-derived MSCs would augment functional .