In vivo effect of bone marrow-derived mesenchymal stem cells in a rat kidney transplantation model with prolonged cold ischemia

Authors

  • Yoshiaki Hara,

    1.  Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Meaghan Stolk,

    1.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Jochen Ringe,

    1.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Tissue Engineering Laboratory, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
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  • Tilo Dehne,

    1.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Tissue Engineering Laboratory, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
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  • Juliane Ladhoff,

    1.  Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Katja Kotsch,

    1.  Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Innsbruck, Austria
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  • Anja Reutzel-Selke,

    1.  Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Petra Reinke,

    1.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Department of Internal Medicine and Nephrology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Hans-Dieter Volk,

    1.  Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Martina Seifert

    1.  Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
    2.  Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
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  • Conflicts of Interest
    The authors have declared no conflicts of interest.

Martina Seifert PhD, Institute of Medical Immunology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1/Föhrerstr. 15, D-13353 Berlin, Germany. Tel.: +49-30-450539435; fax: +49-30-450539902; e-mail: martina.seifert@charite.de

Summary

Brain death and prolonged cold ischemia are major contributors to the poorer long-term outcome of transplants from deceased donor kidney transplants, with an even higher impact if expanded criteria donors (‘marginal organs’) are used. Targeting ischemia-reperfusion injury-related intragraft inflammation is an attractive concept to improve the outcome of those grafts. As mesenchymal stem cells (MSCs) express both immunomodulatory and tissue repair properties, we evaluated their therapeutic efficacy in a rat kidney transplant model of prolonged cold ischemia. The in vitro immunomodulatory capacity of bone marrow-derived rat MSCs was tested in co-cultures with rat lymph node cells. For in vivo studies, Dark Agouti rat kidneys were cold preserved and transplanted into Lewis rats. Syngeneic Lewis MSCs were administered intravenously. Transplants were harvested on day 3, and inflammation was examined by quantitative RT-PCR and histology. Similarly to MSCs from other species, rat MSCs in vitro also showed a dose-dependent immunomodulatory capacity. Most importantly, in vivo administration of MSCs reduced the intragraft gene expression of different pro-inflammatory cytokines, chemokines, and intercellular adhesion molecule-1. In addition, fewer antigen-presenting cells were recruited into the renal allograft. In conclusion, rat MSCs ameliorate inflammation induced by prolonged cold ischemia in kidney transplantation.

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