• Open Access

Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation

Authors

  • W. A. Noort,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
    3. Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands
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    • These authors contributed equally.

  • M. I. F. J. Oerlemans,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
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    • These authors contributed equally.

  • H. Rozemuller,

    1. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
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  • D. Feyen,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
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  • S. Jaksani,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
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  • D. Stecher,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
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  • B. Naaijkens,

    1. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
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  • A. C. Martens,

    1. Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands
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  • H. J. Bühring,

    1. University Clinic of Tübingen, Department of Internal Medicine II, Division of Hematology, Oncology and Immunology, Tübingen, Germany
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  • P. A. Doevendans,

    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
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  • J. P. G. Sluijter

    Corresponding author
    1. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
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Correspondence to: J. P. G. SLUIJTER, Ph.D., Laboratory of Experimental Cardiology, G02.523, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 755 7155 Fax: +31 30 252 2693 E-mail: J.Sluijter@umcutrecht.nl

Abstract

Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune-modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible.

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