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Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair.
ACS Nano ( IF 15.8 ) Pub Date : 2018-12-04 , DOI: 10.1021/acsnano.8b05892 Zhenhua Li 1, 2 , Deliang Shen 3 , Shiqi Hu 1, 2 , Teng Su 1, 2 , Ke Huang 1, 2 , Feiran Liu 1, 2 , Lei Hou 4, 5 , Ke Cheng 1, 2
ACS Nano ( IF 15.8 ) Pub Date : 2018-12-04 , DOI: 10.1021/acsnano.8b05892 Zhenhua Li 1, 2 , Deliang Shen 3 , Shiqi Hu 1, 2 , Teng Su 1, 2 , Ke Huang 1, 2 , Feiran Liu 1, 2 , Lei Hou 4, 5 , Ke Cheng 1, 2
Affiliation
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Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h). Through bioorthogonal click reaction, the two antibodies are linked in vivo, engaging endogenous stem cells with circulating platelets. As a result, the platelets redirect the stem cells to the injured heart. In vitro and in vivo studies demonstrated that bioorthogonal click reaction was able to induce the conjugation of platelets and endothelial progenitor cells (EPCs) and enhance the binding of EPCs to collagen and injured blood vessels. More importantly, in a mouse model of acute myocardial infarction, the in vivo results of cardiac function, heart morphometry, and immunohistochemistry assessment all confirmed effective heart repair by the PTBC system.
中文翻译：
预靶向和生物正交点击化学介导的内源干细胞归巢用于心脏修复。
干细胞疗法是治疗缺血性心脏病的有前途的策略之一。然而，干细胞移植的临床应用因梗塞心肌中的细胞植入量低而受到限制。利用预靶向和生物正交化学的优势，我们设计了预靶向和生物正交化学（PTBC）系统来捕获内源性循环干细胞并将其靶向受损的心脏以进行有效修复。两种生物正交抗体以预靶向间隔（48小时）静脉注射。通过生物正交点击反应，两种抗体在体内连接，使内源干细胞与循环血小板结合。结果，血小板将干细胞重定向到受伤的心脏。体外和体内研究表明，生物正交点击反应能够诱导血小板和内皮祖细胞（EPC）的结合，并增强EPC与胶原蛋白和受损血管的结合。更重要的是，在急性心肌梗死小鼠模型中，体内心脏功能、心脏形态测量和免疫组织化学评估结果均证实了PTBC系统能够有效修复心脏。
更新日期：2018-12-04
中文翻译：
预靶向和生物正交点击化学介导的内源干细胞归巢用于心脏修复。
干细胞疗法是治疗缺血性心脏病的有前途的策略之一。然而，干细胞移植的临床应用因梗塞心肌中的细胞植入量低而受到限制。利用预靶向和生物正交化学的优势，我们设计了预靶向和生物正交化学（PTBC）系统来捕获内源性循环干细胞并将其靶向受损的心脏以进行有效修复。两种生物正交抗体以预靶向间隔（48小时）静脉注射。通过生物正交点击反应，两种抗体在体内连接，使内源干细胞与循环血小板结合。结果，血小板将干细胞重定向到受伤的心脏。体外和体内研究表明，生物正交点击反应能够诱导血小板和内皮祖细胞（EPC）的结合，并增强EPC与胶原蛋白和受损血管的结合。更重要的是，在急性心肌梗死小鼠模型中，体内心脏功能、心脏形态测量和免疫组织化学评估结果均证实了PTBC系统能够有效修复心脏。
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