| Limited immune-modulating activity of porcine mesenchymal stromal cells abolishes their protective efficacy in acute kidney injury. | |
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MedLine Citation:
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PMID: 20143956 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Bärbel Brunswig-Spickenheier; Janna Boche; Christof Westenfelder; Frauke Peimann; Achim D Gruber; Kai Jaquet; Korff Krause; Jozef Zustin; Axel R Zander; Claudia Lange |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Stem cells and development Volume: 19 ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-24 Completed Date: 2010-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: United States |
Other Details:
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Languages: eng Pagination: 719-29 Citation Subset: IM |
Affiliation:
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Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Female Humans Interleukin-6 / biosynthesis Kidney Failure, Acute / therapy* Lymphocyte Culture Test, Mixed Male Mesenchymal Stem Cell Transplantation / methods* Mesenchymal Stem Cells / immunology* Rats Reperfusion Injury Species Specificity Swine Transplantation, Homologous |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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