Erythropoietin Responsive Cardiomyogenic Cells Contribute to Heart Repair Post Myocardial Infarction

被引:23
作者
Zafiriou, Maria Patapia [1 ]
Noack, Claudia [1 ]
Unsoeld, Bernhard [2 ]
Didie, Michael [1 ,2 ]
Pavlova, Elena [1 ]
Fischer, Henrike J. [3 ]
Reichardt, Holger M. [3 ]
Bergmann, Martin W. [4 ]
El-Armouche, Ali [1 ,5 ]
Zimmermann, Wolfram-Hubertus [1 ,6 ]
Zelarayan, Laura Cecilia [1 ]
机构
[1] Univ Gottingen, Univ Med Ctr, HRCG, Inst Pharmacol, D-37075 Gottingen, Germany
[2] Univ Gottingen, Univ Med Ctr, HRCG, Dept Cardiol & Pneumol, D-37075 Gottingen, Germany
[3] Univ Gottingen, Univ Med Ctr, HRCG, Inst Cellular & Mol Immunol, D-37075 Gottingen, Germany
[4] Asklepios Klin St Georg, Dept Cardiol, Hamburg, Germany
[5] Tech Univ Dresden, Fac Med, Dept Pharmacol & Toxicol, Dresden, Germany
[6] German Ctr Cardiovasc Res DZHK, Gottingen, Germany
关键词
Epo-responsive MHC expressing cells; Erythropoietin responsive myosin heavy chain expressing cells; Myocardial regeneration; Erythropoietin; Ischemia; PERCUTANEOUS CORONARY INTERVENTION; ERYTHROID PROGENITOR CELLS; ISCHEMIC-HEART; STEM-CELLS; REAL-TIME; RECEPTOR; EXPRESSION; DIFFERENTIATION; CARDIOMYOCYTES; TRIAL;
D O I
10.1002/stem.1741
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function.
引用
收藏
页码:2480 / 2491
页数:12
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