• Open Access

Erythropoietin Responsive Cardiomyogenic Cells Contribute to Heart Repair Post Myocardial Infarction

Authors

  • Maria Patapia Zafiriou,

    Corresponding author
    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
    • Correspondence: Laura Cecilia Zelarayán, Ph.D., Institute of Pharmacology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen 37075, Germany. Telephone: 49-551-39-5777; Fax: 49–551-39-5699; e-mail: laura.zelarayan@med.uni-goettingen.de; or Maria Patapia Zafiriou, Ph.D., Institute of Pharmacology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen 37075, Germany. Telephone: 49–551-39–5777; Fax: 49-551-39-5699; e-mail: patapia.zafeiriou@med.uni-goettingen.de

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  • Claudia Noack,

    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Bernhard Unsöld,

    1. Department of Cardiology and Pneumology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Michael Didie,

    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
    2. Department of Cardiology and Pneumology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Elena Pavlova,

    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Henrike J. Fischer,

    1. Institute of Cellular and Molecular Immunology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Holger M. Reichardt,

    1. Institute of Cellular and Molecular Immunology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
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  • Martin W. Bergmann,

    1. Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany
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  • Ali El-Armouche,

    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
    2. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Technology-Dresden, Germany
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  • Wolfram-Hubertus Zimmermann,

    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
    2. German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
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  • Laura Cecilia Zelarayan

    Corresponding author
    1. Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany
    • Correspondence: Laura Cecilia Zelarayán, Ph.D., Institute of Pharmacology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen 37075, Germany. Telephone: 49-551-39-5777; Fax: 49–551-39-5699; e-mail: laura.zelarayan@med.uni-goettingen.de; or Maria Patapia Zafiriou, Ph.D., Institute of Pharmacology, Heart Research Center Göttingen (HRCG), University Medical Center, Georg-August-Universität Göttingen, Göttingen 37075, Germany. Telephone: 49–551-39–5777; Fax: 49-551-39-5699; e-mail: patapia.zafeiriou@med.uni-goettingen.de

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Abstract

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. Stem Cells 2014;32:2480–2491

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