间充质干细胞外泌体移植治疗缺血性心脏病  

Mesenchymal stem cell-derived exosome transplantation for ischemic heart disease

作　　者：刘东月 王宪云[2,3,4] 王乐 郑明奇[1,2,3] 尹亚娟 杨佳炜[1,2,3] 丁理妮 刘刚 Liu Dongyue;Wang Xianyun;Wang Le;Zheng Mingqi;Yin Yajuan;Yang Jiawei;Ding Lini;Liu Gang(Department of Cardiovascular Medicine,First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei Province,China;Hebei International Joint Research Center for Structural Heart Disease,Shijiazhuang 050031,Hebei Province,China;Hebei Provincial Key Laboratory of Heart and Metabolism,Shijiazhuang 050031,Hebei Province,China;Cell Therapy Laboratory,First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei Province,China)

机构地区：[1]河北医科大学第一医院心血管内科,河北省石家庄市050031 [2]河北医科大学第一医院细胞治疗实验室,河北省石家庄市050031 [3]河北省结构性心脏病国际联合研究中心,河北省石家庄市050031 [4]河北省心脏与代谢重点实验室,河北省石家庄市050031

出　　处：《中国组织工程研究》2023年第15期2435-2442,共8页Chinese Journal of Tissue Engineering Research

基　　金：河北省科技支撑计划重点项目(203777117D),项目负责人:刘刚;河北省外国引进智力项目(YZ202001),项目负责人:刘刚;河北省自然科学青年基金项目(C2018206037),项目负责人:王宪云;精准医学联合基金重点项目(H2021206399),项目负责人:郑明奇;精准医学联合基金培育项目(H2021206031),项目负责人:王乐;河北省引进留学人员资助项目(C20210347),项目负责人:王宪云。

摘　　要：背景:缺血性心脏病是严重威胁人类生命健康的疾病类型之一,而干细胞分泌的外泌体已经在缺血性心脏病的治疗中展示出良好的效果和应用前景,并取得了重要研究进展。目的:就间充质干细胞外泌体移植治疗缺血性心脏病的疗效、作用机制、优化方案和移植策略分别予以阐述。方法:第一作者于2021年2月应用计算机在PubMed数据库检索1973年1月至2022年3月相关文献,以“mesenchymal stem cell,exosomes,Ischemic heart disease”为英文检索词,最终纳入英文文献88篇文献进行分析。结果与结论:①干细胞分泌的外泌体为细胞外囊泡的重要组分之一,是干细胞发挥功能调节的关键组分,且已经在缺血性心脏病方面展示出良好的治疗效果和应用前景。②间充质干细胞分泌的外泌体可促进缺血损伤心肌组织的血管生成和心肌保护作用、抑制心脏纤维化和改善免疫调节等,进而促进心肌修复和心功能改善。③通过基因工程修饰、miRNA修饰、药物或物理条件预处理以及提高外泌体产量等手段可对干细胞外泌体的产量或功能特性等进行优化,以提高其对缺血性心脏病的治疗效果。④利用生物材料运载外泌体、两步递送法、外泌体喷雾技术或细胞膜修饰外泌体等外泌体移植优化策略,可有效提高间充质干细胞外泌体在损伤心肌组织的滞留率,从而增强其对缺血性心脏病的治疗效果。BACKGROUND:Ischemic heart disease is one type of disease that seriously threatens human life and health.Mesenchymal stem cells derived exosomes have shown obvious therapeutic effects and application prospects in ischemic heart disease,and make important research progress.OBJECTIVE:To review the therapeutic effect of mesenchymal stem cells derived exosomes for ischemic heart disease,repair mechanisms,optimized plan and improved transplantation strategy.METHODS:The relevant articles published from January 1973 to March 2022 were searched in PubMed by the first author in February 2021.The English key words were“mesenchymal stem cell,exosome,ischemic heart disease”.Finally,88 articles were included and analyzed.RESULTS AND CONCLUSION:(1)Exosomes secreted by stem cells are one of the most important components of stem cell excretion to play functional regulation which have shown obvious therapeutic effects and application prospects in ischemic heart disease.(2)Mesenchymal stem cells derived exosomes can promote the angiogenesis and protect ischemia-injured myocardial tissue,inhibit cardiac fibrosis and improve immune regulation,finally promote myocardial repair and the improvement of cardiac function.(3)The production or functional properties of mesenchymal stem cells derived exosomes can be optimized by genetic engineering modification,miRNA modification,pretreated of drugs or physical intervention,and improve exosome production,so as to improve their therapeutic effect on ischemic heart disease.(4)Using biomaterials to carry exosomes,two-step delivery method,exosome spray technology or cell membrane modified exosomes and other exosome transplantation optimization strategies can effectively improve the retention rate of mesenchymal stem cell-derived exosomes in injured myocardial tissue,thereby enhancing their therapeutic effect on ischemic heart disease.

关 键 词：缺血性心脏病 间充质干细胞 外泌体 血管生成 纤维化 修复机制 优化策略 移植策略 

分 类 号：R453[医药卫生—治疗学] R363[医药卫生—临床医学] R364