药物联合MSCs移植趋化CXCR4+骨髓干细胞群持久靶向归巢修复梗死心肌及其机制研究

项目名称： 药物联合MSCs移植趋化CXCR4+骨髓干细胞群持久靶向归巢修复梗死心肌及其机制研究

项目编号： No.81200108

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 宋雷

作者单位： 中国医学科学院阜外心血管病医院

项目金额： 23万元

中文摘要： 本研究基于前期"他汀提高骨髓间充质干细胞（MSCs）移植疗效"的突破性发现,以及MSCs/心肌细胞可旁分泌SDF-1且CXCR4+干细胞群具有强SDF-1趋化性的特点，提出"药物联合MSCs移植可趋化骨髓CXCR4+干细胞群持久性地靶向归巢修复梗死心肌"的假说。拟体外观察SDF-1表达增强剂白藜芦醇（RSV）及代谢抑制剂西格列汀对MSCs在缺血缺氧下分泌SDF-1的影响；建立猪急性心肌梗死（AMI）模型，随机接受骨髓MSCs移植联合：阿托伐他汀(Ator)、Ator+RSV、Ator+西格列汀或Ator+两药合用。在梗死后1周及6周检测SDF-1水平、心肌内移植MSCs数量及靶向归巢的CXCR+干细胞数量、心肌灌注/代谢及心功能变化，可望验证上述假说，并初步阐明药物联合MSCs移植对SDF-1诱导干细胞趋化作用的影响及其机制，对干细胞研究进一步深入及移植疗效的提高有重大科学意义及临床价值。

中文关键词： 间充质干细胞；急性心肌梗死；细胞迁移；基质细胞衍生因子1；趋化因子受体4

英文摘要： Based on our previous finding of Statins improving the effect of MSCs transplantation, the SDF-1 paracrine effect of MSCs/myocardial cells and the CXCR4+ stem cells' chemotaxis to SDF-1, we hypothesize that "Durgs combination with MSCs transplantation could persistently promote chemotaxis of bone marrow CXCR4+ stem cells' targeted homing to repair the infarcted myocardium". SDF-1 expression activator Resveratrol (RSV) and metablism inhabitor Sitagliptin are added to test their influence on MSCs in hypoxia/ischemia condition in vitro.Swine AMI model were created and randomized to Atorvastation (Ator), Ator+RSV, Ator+Sitagliptin, Ator+ RSV+Sitagliptin groups, combined with bone MSCs transplantation. The SDF-1 level, the quantity of implanted MSCs and targeted homing CXCR4+ stem cells, the myocardial perfusion, metablism and heart function will be evaluated and compared among groups in 1 and 6 weeks post infarction.Certify the above hyposis and clarify the mechanism of SDF-1 induced stem cells chemotaxis, has both scientific significance and application values for further study of stem cells and facilitating its therapeutic effect.

英文关键词： Mesenchymal stem cells；Acute myocardial infarction；Cell mobilization；SDF-1；CXCR4