Fachbereich Veterinärmedizin



    Limited Immune-modulating Activity of Porcine Mesenchymal Stromal Cells Abolishes their Protective Efficacy in Acute Kidney Injury (2010)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Brunswig-Spickenheier, Bärbel
    Boche, Janna
    Westenfelder, Christof
    Peimann, Frauke
    Gruber, Achim D
    Jaquet, Kai
    Krause, Korff
    Zustin, Jozef
    Zander, Axel R
    Lange, Claudia
    Stem cells and development; 19(5) — S. 719–729
    ISSN: 1547-3287
    DOI: 10.1089/scd.2009.0494
    Pubmed: 20143956
    Institut für Tierpathologie

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    Abstract / Zusammenfassung

    We demonstrated previously that administration of mesenchymal stromal cells (MSCs) after renal ischemia/reperfusion injury (IRI) in rats protected renal function and hastened repair through complex paracrine mechanisms. Here we investigated kidney-protective actions of MSCs in a porcine IRI model that may have relevance to human acute kidney injury (AKI). Groups of female pigs with bilateral IRI were infused with autologous or male allogeneic MSCs. No acute or late complications were observed, but unexpectedly, MSC therapy also had no beneficial effects on kidney function and histology. In vitro, we demonstrated substantial functional and phenotypic overlaps between rodent, human, and porcine MSCs, all of which exhibited trilineage differentiation, characteristic antigen profiles, and secretion of renoprotective vascular endothelial growth factor (VEGF)-A and insulin-like growth factor-1 (IGF-1). However, in striking contrast to human MSCs, porcine MSCs failed to inhibit the mixed lymphocyte reaction (MLR) and induced robust production of proinflammatory interleukin-6 (IL-6). In summary, in contrast to rodent models, treatment of porcine IRI with MSCs was not kidney-protective. This, we conclude, is due to the fact that porcine MSCs exert inadequate immune-modulating effects, further demonstrating that successful therapy of IRI with MSCs critically depends on their anti-inflammatory actions. As a consequence, treatment of AKI with MSCs is not informative regarding the investigation of the underlying mechanisms in this large animal model. We expect, however, that the treatment of human IRI of the kidney with immune-modulating MSCs will be as effective as in rodent models.