Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury
Autor: | A.-M. Faussat, L. Behr, M. Hekmati, Nicolas Borenstein, L.-H. Noel, A. Lucchini, M. Lelievre-Pegorier, K. Laborde, K. Houcinet |
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Rok vydání: | 2009 |
Předmět: |
Pathology
medicine.medical_specialty Necrosis medicine.medical_treatment Kidney Stem cell marker Polymerase Chain Reaction chemistry.chemical_compound medicine Animals Cell Proliferation DNA Primers Sheep Base Sequence business.industry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Original Articles Cell Biology General Medicine medicine.disease Vascular endothelial growth factor Transplantation Disease Models Animal medicine.anatomical_structure Cytokine chemistry Reperfusion Injury Immunology medicine.symptom business Reperfusion injury Stem Cell Transplantation |
Zdroj: | Cell Prolif |
ISSN: | 1365-2184 0960-7722 |
DOI: | 10.1111/j.1365-2184.2009.00591.x |
Popis: | 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. |
Databáze: | OpenAIRE |
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