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Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates

文献类型：期刊论文

作者Zhu, Keyang1,2; Ni, Cheng1,2; Zhong, Zhiwei1,2; Wu, Yan1,2; Wang, Yingchao1,2; Xu, Yinchuan1,2; Yang, Qian2; Li, Qingju1,2; Zhao, Jing1,2; Chen, Jinghai1,2
刊名CIRCULATION RESEARCH
出版日期2018
卷号122期号:7页码:958-969
ISSN号0009-7330
关键词human embryonic stem cells immunosuppression primates transplantation
DOI10.1161/CIRCRESAHA.117.311578
文献子类Article
英文摘要Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: The main of this study is to clarify whether hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus monkeys that had received intramyocardial injections of 1x10(7) EGFP (enhanced green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group). Methods and Results: Measurements of EGFP gene levels and EGFP immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was greater in the MI+MDR+CVPC group than that in the MI+cyclosporine+CVPC group. However, even in the MI+MDR+CVPC group, no transplanted cells could be detected at 140 days after transplantation. Concomitantly, immunofluorescent analysis of CD3, CD4, and CD8 expression indicated that T-lymphocyte infiltration in the CVPC-transplanted hearts was less in the MDR-treated animals than in the cyclosporine-alone-treated animals. The recovery of left ventricular function on day 28 post-MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR group, although both immunosuppression regimens were associated with transient hepatic dysfunction. Conclusions: This is the largest study of hPSCs in nonhuman primates in cardiovascular field to date (n=32). Compared with cyclosporine alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in primates; this is associated with less apoptosis of native cardiac cells and better recovery of left ventricular function at 28 days. However, even with MDR, transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after transplantation, thereby excluding remuscularization as a mechanism for the functional effect.
学科主题Cardiovascular System & Cardiology ; Hematology
WOS关键词RENAL-TRANSPLANTATION ; CARDIAC PROGENITORS ; HEART-FAILURE ; RAT HEARTS ; CYCLOSPORINE ; INDUCTION ; TOXICITY ; BASILIXIMAB ; DERIVATIVES ; SURVIVAL
语种英语
出版者LIPPINCOTT WILLIAMS & WILKINS
WOS记录号WOS:000428709500015
版本出版稿
源URL[http://202.127.25.144/handle/331004/591]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Cardiovasc Key Lab Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China;
2.Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou, Zhejiang, Peoples R China;
3.Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Cardiovasc Surg, Hangzhou, Zhejiang, Peoples R China;
4.Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Lab Med, Hangzhou, Zhejiang, Peoples R China;
5.Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Anesthesiol, Hangzhou, Zhejiang, Peoples R China;
6.Univ CAS, Chinese Acad Sci CAS Shanghai, Shanghai Inst Biol, Key Lab Stem Cell Biol,Inst Hlth Sci, Beijing, Peoples R China;
7.Univ CAS, Chinese Acad Sci CAS Shanghai, Shanghai Inst Biol, Lab Mol Cardiol,Inst Hlth Sci, Beijing, Peoples R China;
8.Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL USA,
推荐引用方式
GB/T 7714		 Zhu, Keyang,Ni, Cheng,Zhong, Zhiwei,et al. Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates[J]. CIRCULATION RESEARCH,2018,122(7):958-969.
APA Zhu, Keyang.,Ni, Cheng.,Zhong, Zhiwei.,Wu, Yan.,Wang, Yingchao.,...&,.(2018).Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.CIRCULATION RESEARCH,122(7),958-969.
MLA Zhu, Keyang,et al."Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates".CIRCULATION RESEARCH 122.7(2018):958-969.

入库方式： OAI收割

来源：上海营养与健康研究所

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