Publikationsdatenbank

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

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Brunswig-Spickenheier, Bärbel

Boche, Janna

Westenfelder, Christof

Peimann, Frauke

Gruber, Achim D

Jaquet, Kai

Krause, Korff

Zustin, Jozef

Zander, Axel R

Lange, Claudia

Quelle

Stem cells and development

Bandzählung: 19

Heftzählung: 5

Seiten: 719 – 729

ISSN: 1547-3287

Sprache

Englisch

Verweise

DOI: 10.1089/scd.2009.0494

Pubmed: 20143956

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

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.