超声介导载基因微泡调动SDF-1/CXCR4轴和BMP2动员AMI大鼠内源性BMSCs向心脏归巢分化

项目名称： 超声介导载基因微泡调动SDF-1/CXCR4轴和BMP2动员AMI大鼠内源性BMSCs向心脏归巢分化

项目编号： No.81460266

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 穆玉明

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 目前骨髓干细胞移植用于治疗急性心肌梗死已成为极具前景的治疗手段。但需要经周围静脉、冠状动脉或心肌直接注射等方式进行移植。存在干细胞分离、纯化、传代并确保不被污染的技术要求。并都存在着干细胞靶向归巢困难，向心肌组织分化数量有限等问题，诸多的原因使外源性干细胞移植治疗心肌梗死改善心功能的疗效有限。本研究通过建立大鼠急性心肌梗死模型，采用亲和素-生物素桥接法制备携带干细胞动员剂（SDF-1a）和干细胞心肌分化诱导剂（BMP2)双基因的脂质微泡,利用超声靶向破坏微泡定位释放技术,实现心肌梗死区域SDF-1和BMP2的过表达，发挥两者的联合作用，通过调动SDF-1/CXCR4生物轴，招募内源性的表达CXCR4受体的干细胞向心脏归巢，并向心肌组织分化。进而评价这种在体自我移植，定向分化治疗心肌梗死的可行性，期望为急性心肌梗死干细胞治疗提供一种新的治疗方法。

中文关键词： 急性心肌梗死；超声介导；载基因微泡；自体干细胞动员；归巢分化

英文摘要： At present bone marrow stem cells transplantation has become a promising treatment for myocardial infarction. However, exogenous bone marrow stem cell transplantation need delivery of stem cells through intraveous, coronary artery or intramyocardial injection and face technical issue there is no pollution during isolation, purification and transfer of stem cells.This method have limited efficacy in treatment for myocardial infarction because the number of exogenous stem cells homing to the ischemia myocardium and differentiating into myocardial cell is limited. The present study is to establish a rat model of acute myocardial infarction and use ultrasound-targeted microbubble destruction which carring SDF-1 and BMP2 and realize over expression of SDF-1and BMP2 in myocardial infarction area. Combination of SDF-1and BMP2 will transfer the SDF - 1 / CXCR4 biological axis which recruit endogenous stem cell homing to the ischemia myocardium and differentiating into myocardial cell. We expect provide a new treatment for acute myocardial infarction in stem cell therapy.

英文关键词： AMI;ultrasound mediated;loading gene microbubble;mobilize;homing and differentiation