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Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury

Authors

  • L. Behr,

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
    2. IMM-RECHERCHE, 42 boulevard Jourdan, Paris, France
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  • M. Hekmati,

    1. IMM-RECHERCHE, 42 boulevard Jourdan, Paris, France
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  • A. Lucchini,

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
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  • K. Houcinet,

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
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  • A.-M. Faussat,

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
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  • N. Borenstein,

    1. IMM-RECHERCHE, 42 boulevard Jourdan, Paris, France
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  • L.-H. Noel,

    1. INSERM U574, Hospital Necker-Enfant-Malades, University Paris Descartes F-75006, France
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  • M. Lelievre-Pegorier,

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
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  • K. Laborde

    1. INSERM, U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie – Paris 6, UMR S872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France
    2. Division of Physiology, Hospital Necker Enfants-Malades, University Paris Descartes F-75006, France
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  • Institutions where the work has been carried out:
    1. All in vivo experiments (together with the functional evaluation) have been carried out at IMM-RECHERCHE, Institut Mutualiste Montsouris, 75014 Paris.
    2. Histological analysis has been performed at INSERM U574, Hospital Necker-Enfant-Malades, University Paris Descartes F-75006, France.
    3. Real-time polymerase chain reaction analysis has been carried out at INSERM U872, Centre de Recherche des Cordeliers, Paris, F-75006 France; Université Pierre et Marie Curie, Paris 6, UMR S872, Paris, F-75006 France; and Université Paris Descartes, UMR S 872, Paris, F-75006 France.

L. Behr, IMM-Recherche, Institut Mutualiste Montsouris, 42, boulevard Jourdan, 75014 Paris, France. Tel.: +33 1 56 61 68 22, Fax: +33 1 56 61 67 40; E-mail: luc.behr@imm.fr

Abstract

Objectives: Adult mesenchymal stem cells (MSC) have been proven to be of benefit to the kidney in different experimental models of renal injuries. All studies have been performed in valuable rodent models, but the relevance of these results to large mammals and ultimately, to humans remains unknown. Therefore, the aim of this study was to investigate the effect of MSC transplantation in an alternative ovine large-animal model of bilateral kidney ischaemia reperfusion injury.

Material and methods: Sheep were divided into three groups: one sham-operated group and two groups submitted to renal bilateral ischaemia for 60 min. Animals with ischaemia reperfusion injury were treated with injection of autologous MSCs or with vehicle medium.

Results: The model sheep presented with renal histological manefestations that closely resembled lesions seen in patients. Transplanted MSCs were found in glomeruli but not in tubules and did not express glomerular cell markers (podocin, von Willebrand factor), but functional evaluation showed no beneficial effect of MSC infusion. Morphological and molecular analyses corroborated the functional results. MSCs did not repair kidney parenchyma and failed to modulate cell death and proliferation or cytokine release (tumour necrosis factor-alpha, vascular endothelial growth factor alpha (VEGF-α), Bcl-2, caspase).

Conclusion: In this unique autologous large-animal model, MSCs did not exhibit reparative or paracrine protective properties.

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