Life-Sparing Effect of Human Cord Blood-Mesenchymal Stem Cells in Experimental Acute Kidney Injury

Authors

  • Marina Morigi,

    Corresponding author
    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
    • “Mario Negri” Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy
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    • Telephone: +39-035-319-888; Fax: +39-035-319-331

  • Cinzia Rota,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Tiziana Montemurro,

    1. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Elisa Montelatici,

    1. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Viviana Lo Cicero,

    1. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Barbara Imberti,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Mauro Abbate,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Carla Zoja,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Paola Cassis,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Lorena Longaretti,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Paolo Rebulla,

    1. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Martino Introna,

    1. Laboratory of Cell Therapy “G. Lanzani,” Ospedali Riuniti di Bergamo, Bergamo, ItalyUnit of Hematology and Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy
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  • Chiara Capelli,

    1. Laboratory of Cell Therapy “G. Lanzani,” Ospedali Riuniti di Bergamo, Bergamo, ItalyUnit of Hematology and Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy
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  • Ariela Benigni,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
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  • Giuseppe Remuzzi,

    1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy
    2. Laboratory of Cell Therapy “G. Lanzani,” Ospedali Riuniti di Bergamo, Bergamo, ItalyUnit of Hematology and Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy
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  • Lorenza Lazzari

    1. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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  • Author contributions: M.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; C.R.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; T.M.: provision of study material, collection and/or assembly of data; E.M.: provision of study material, collection and/or assembly of data; V.L.C.: provision of study material, collection and/or assembly of data; B.I.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; M.A.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; C.Z.: collection and/or assembly of data, data analysis and interpretation; P.C.: collection and/or assembly of data; L. Longaretti: collection and/or assembly of data; P.R.: provision of study material, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; M.I.: provision of study material and data analysis and interpretation; C.C.: provision of study material; A.B.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; G.R.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; L. Lazzari: provision of study material, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript. M.M. and C.R. contributed equally to this article.

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

  • First published online in STEM CELLSEXPRESS January 4, 2010.

Abstract

In search for new sources of mesenchymal stem cells (MSCs) for renal repair in acute kidney injury (AKI), we investigated the potential of human cord blood (CB)-MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with cisplatin-induced AKI ameliorated both renal function and tubular cell injury, and prolonged survival. Transplanted CB-MSCs localized in peritubular areas, limited capillary alterations and neutrophil infiltration. Apoptosis reduced and tubular cell proliferation increased by virtue of stem cell capacity to produce growth factors. The reno-protective effect of CB-MSCs was further confirmed by their ability to inhibit oxidative damage and to induce the prosurvival factor Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production of growth factors and inhibited IL-1β and TNFα synthesis when cocultured with damaged proximal tubular cells indicates a regenerative and anti-inflammatory action of stem cell treatment. Altogether these results highlight the potential of human CB-MSCs as future cell therapy for testing in human AKI. STEM CELLS 2010;28:513–522

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