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Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization

查看全文 作　　者：Peier [1]Chen;Xiaodong [1]Ning;Weirun [1]Li;Yuxuan [1]Pan;Ling [2]Wang;Hekai [1]Li;Xianglin [1]Fan;Jiexin [1]Zhang;Tiantian [1]Luo;Yaobin [3]Wu;Caiwen [1]Ou;Minsheng [1]Chen 高影响力作者 机构地区：[1]Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease,Department of Cardiology and Laboratory of Heart Center,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure,Zhujiang Hospital,Southern Medical University,Guangzhou,510280,China;[2]Biomaterials Research Center,School of Biomedical Engineering,Southern Medical University,Guangzhou,510515,China;[3]Guangdong Engineering Research Center for Translation of Medical 3D Printing Application,Guangdong Provincial Key Laboratory of Medical Biomechanics,National Key Discipline of Human Anatomy,School of Basic Medical Sciences,Southern Medical University,Guangzhou,510515,China高影响力机构 出　　处：《Bioactive Materials》索引2022年第7卷第8期,共14页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation of China(No.81971765,31771060,31671025,81871504,32171355 and 82172103). 摘　　要：Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization. 关 键 词：Artificial stem cells EXOSOMES Myocardial infarction Coronary collateralization
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