Human Cardiac Progenitor Cell Grafts as Unrestricted Source of Supernumerary Cardiac Cells in Healthy Murine Hearts§

Authors

  • Giancarlo Forte,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
    2. Biomaterials Center, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan
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  • Stefano Pietronave,

    1. Dipartimento di Scienze Mediche, Università Piemonte Orientale “A. Avogadro”, Novara, Italy
    2. Japanese-Italian Tissue Engineering Laboratory (JITEL), Tokyo Women's Medical University-Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns), Tokyo, Japan
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  • Giorgia Nardone,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
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  • Andrea Zamperone,

    1. Dipartimento di Scienze Mediche, Università Piemonte Orientale “A. Avogadro”, Novara, Italy
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  • Eugenio Magnani,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
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  • Stefania Pagliari,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
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  • Francesca Pagliari,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
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  • Cristina Giacinti,

    1. Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Universita'“La Sapienza”, Roma, Italy
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  • Carmine Nicoletti,

    1. Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Universita'“La Sapienza”, Roma, Italy
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  • Antonio Musaró,

    1. Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Universita'“La Sapienza”, Roma, Italy
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  • Mauro Rinaldi,

    1. Azienda Ospedaliero-Universitaria San Giovanni Battista, Divisione di Cardiochirurgia, Università degli Studi di Torino, Torino, Italy
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  • Marco Ribezzo,

    1. Azienda Ospedaliero-Universitaria San Giovanni Battista, Divisione di Cardiochirurgia, Università degli Studi di Torino, Torino, Italy
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  • Chiara Comoglio,

    1. Azienda Ospedaliero-Universitaria San Giovanni Battista, Divisione di Cardiochirurgia, Università degli Studi di Torino, Torino, Italy
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  • Enrico Traversa,

    1. Biomaterials Center, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan
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  • Teruo Okano,

    1. Japanese-Italian Tissue Engineering Laboratory (JITEL), Tokyo Women's Medical University-Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns), Tokyo, Japan
    2. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWMU), Tokyo, Japan
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  • Marilena Minieri,

    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
    2. Japanese-Italian Tissue Engineering Laboratory (JITEL), Tokyo Women's Medical University-Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns), Tokyo, Japan
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  • Maria Prat,

    1. Dipartimento di Scienze Mediche, Università Piemonte Orientale “A. Avogadro”, Novara, Italy
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  • Paolo Di Nardo

    Corresponding author
    1. Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy
    2. Japanese-Italian Tissue Engineering Laboratory (JITEL), Tokyo Women's Medical University-Waseda University Joint Institution for Advanced Biomedical Sciences (TWIns), Tokyo, Japan
    • Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier, 1, Roma 00133, Italy
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    • Tel.: +39-06-72594215; Fax: +39-06-2024130/72594263


  • Author contributions: G.F. and S.P.: human cell extraction, culture, and cell sheet characterization; F.P., G.N., E.M., and A.Z.: human cell culture, differentiation, and cell sheet preparation; C.G., C.N., and A.M.: cell sheet in vivo implants; T.O., M.M., E.T., M.P., and P.D.N.: experimental design, discussion, and manuscript editing; and M.R., C.C., and M.R.: surgical specimens harvesting and treatment. G.F., S.P., M.P., and P.D.N. contributed equally in the respective roles.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS October 21, 2011.

Abstract

Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures.

The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy. STEM CELLS 2011;29:2051–2061.

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