新型双功能超声微泡增效CD47高表达的骨髓间充质干细胞干预心肌纤维化的研究

项目名称： 新型双功能超声微泡增效CD47高表达的骨髓间充质干细胞干预心肌纤维化的研究

项目编号： No.81201101

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 邓玮

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 病理性心肌纤维化是缺血性心脏病向心衰发展的必经阶段。干细胞移植给心肌纤维化的治疗带来了新的希望，但是干细胞移植效率低下是心肌成形术中面临的瓶颈问题。本研究拟将脂质微泡作为载体，通过共价结合法将抗肌凝蛋白轻链抗体（AMCLA）及CD29抗体装配在脂质微泡上，制备能导引骨髓间充质干细胞至损伤靶位的新型双功能免疫脂质微泡制剂。在超声辐照新型微泡辅助下，静脉输入CD47高表达的间充质干细胞，观察优化干细胞和促进靶向归巢后对移植效率的改善及心肌纤维化的干预效果。CD47是能躲避免疫细胞吞噬的"细胞免死"标志，高表达CD47的间充质干细胞获有"特赦"标志；双功能免疫脂质微泡可望具有主动寻靶、特异性黏附于损伤心肌的能力，二者联合应用试图延长干细胞移植后的存活时间并促进靶向归巢。本研究着力于改善干细胞移植效率低、归巢量少的缺陷，将为提高干细胞移植效率提供新的思路。

中文关键词： CD47；骨髓间充质干细胞；心肌纤维化；归巢；双功能超声微泡

英文摘要： Pathological myocardial fibrosis is the necessary stage in the progression of ischemic heart disease to heart failure. Stem cells have showed unique advantages in the treatment of myocardial fibrosis in recent years. However, inefficient stem cell transplantation is the bottleneck in cellular cardiomyoplasty. This study intends to use lipid microbubbles as a carrier, assemble the anti-myosin light chain antibody (AMLCA) and CD29 antibody onto the lipid microbubbles by covalent binding method, and thus prepare a new bifunctional echogenic immunoliposomes preparation which could guide mesenchymal stem cells to the injured target.With the aid of new ultrasonic wave irradiated microbubbles, intravenous infusion of mesenchymal stem cells with CD47 high expression to observe the improvement of transplantation efficiency and intervention effect on myocardial fibrosis after optimization of the "seed" and "soil".CD47 is the cell marker to evade phagocytosis by the immune system, mesenchymal stem cells with CD47 high expression are with the "amnesty" sign;Bifunctional echogenic immunoliposomes are expected to have the capability to find target initiatively and specific adhesion to the injured myocardium, the combination of the two functions are expected to prolong the survival time of stem cell after transplantation and

英文关键词： CD47；bone marrow mesenchymal srem cells；myocardial fibrosis；homing；bifunctional echogenic microbubbles