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Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model

Mesenchymal stem cell sheet transplantation combined with lo...

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2012年浙江省骨科学术年会

作者： Jianwei Wang Yiying Q Tengfei Zhao Weiqi Yan Kan Xu Zhongli Shi Department of Orthopedic Surgery the Second Affiliated Hospital School of Medicine Zhejiang University

Nonunion of fractured bones is a common clinical problem for orthopedic surgeons. This study aimed to investigate the effects of simvastatin locally applied from calcium sulphate (CS) combined with mesenchymal stem cell (msc) sheet on fracture healing. In vitro, the proliferation and differentiation of rat bone marrow derived mscs stimulated by simvastatin were investigated. In vivo, an osteotomy model was made in rat tibia and fractured tibias were treated with CS, CS/simvastatin, CS/msc sheet or simvastatin-loaded CS with msc or untreated (control). Tibias were harvested at 2 or 8 weeks and underwent RT-PCR, X-ray, micro-CT and histological analysis. The expression levels of BMP-2, ALP, OCN, OPG and VEGF of simvastatin-induced mscs increased with the concentrations of the simvastatin, significantly higher than those in the mscs group. At 2 weeks, the CS/simvastatin/msc sheet group showed significantly higher expressions of BMP-2, ALP, OCN, OPG and VEGF;more callus formation around the fracture site compared with other four groups. At 8 weeks, complete bone union was obtained in the CS/simvastatin/msc sheet group. By contrast, new regenerated bone tissue partially bridged the gap in the CS/simvastatin group and CS/msc sheet group;the control and CS group showed nonunion of the tibia. These results showed that both simvastatin and msc sheet contributed to the formation of new bone and the tibia fracture was completely cured by transplantation of msc sheet with locally applied simvastatin. Such msc sheet with locally applied simvastatin may contribute to the treatment of fractures, nonunion bone defects in clinic.

关键词： simvastatin mesenchymal stem cells msc sheet bone formation nonunion

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