Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury
Autor: | Marilda Mazzali, Alvaro Pacheco-Silva, Felipe Caetano Beraldo, Vicente de Paula Antunes Teixeira, Gabriela Filoso Barnabe, Luis Eugenio A. de Mello, Pamella Huey Mei Wang, Patricia Semedo, Niels Olsen Saraiva Camara, Telma T. Schwindt, Marlene Antônia dos Reis, Fabiana Louise Motta |
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Rok vydání: | 2009 |
Předmět: |
Male
Nervous system Cerebellum Physiology Ischemia Pharmacology Kidney chemistry.chemical_compound Neurosphere Precursor cell otorhinolaryngologic diseases Genetics medicine Animals Rats Wistar Neurons Creatinine business.industry General Medicine medicine.disease Rats stomatognathic diseases medicine.anatomical_structure chemistry Nephrology Reperfusion Injury Immunology Stem cell business Stem Cell Transplantation |
Zdroj: | Nephron Experimental Nephrology. 112:e20-e28 |
ISSN: | 1660-2129 |
Popis: | In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to immunomodulation. To this end, Wistar rats (200–250 g) were submitted to 1-hour ischemia and treated with NPCs (4 × 106 cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with carboxyfluorescein diacetate succinimydylester (CFSE). Kidneys were harvested for analysis of cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78mg/dl, p < 0.05) and acute tubular necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-CFSE and glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker) mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-β and TNF-α expression and higher anti-inflammatory IL-4 and IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory cytokines (IL-1β, TNF-α and INF-γ). Our data suggested that NPC therapy improved renal function by influencing immunological responses. |
Databáze: | OpenAIRE |
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