Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

Author Wang, Pamella Huey Mei Autor UNIFESP Google Scholar
Schwindt, Telma Tiemi Autor UNIFESP Google Scholar
Barnabe, Gabriela Filoso Autor UNIFESP Google Scholar
Motta, Fabiana Louise Teixeira Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Beraldo, Felipe Caetano Google Scholar
Mazzali, Marilda Google Scholar
Reis, Marlene Antonia dos Google Scholar
Teixeira, Vicente de Paula Antunes Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Mello, Luiz Eugenio Araujo de Moraes Autor UNIFESP Google Scholar
Camara, Niels Olsen Saraiva Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Univ Fed Triangulo Mineiro
Inst Israelita Ensino & Pesquisa Albert Einstein
Abstract 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 x 10(6) 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-beta and TNF-alpha 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-1 beta, TNF-alpha and INF-gamma). Our data suggested that NPC therapy improved renal function by influencing immunological responses. Copyright (C) 2009 S. Karger AG, Basel
Keywords Neurospheres
Neural precursor cells
Ischemia and reperfusion injury, renal
Immunomodulation
Language English
Sponsor MCT/CT-Saude/Decit/SCTIE/MS
Fundacao de Apoio a Pesquisa do Estado de São Paulo
Grant number MCT/CT-Saude/Decit/SCTIE/MS: 552307/2005-0
Fundacao de Apoio a Pesquisa do Estado de São Paulo: 04/08311-6
Fundacao de Apoio a Pesquisa do Estado de São Paulo: 04/13826-5
Fundacao de Apoio a Pesquisa do Estado de São Paulo: 05/50085-6
Fundacao de Apoio a Pesquisa do Estado de São Paulo: 07/07139-3
Date 2009-01-01
Published in Nephron Experimental Nephrology. Basel: Karger, v. 112, n. 1, p. E20-E28, 2009.
ISSN 1660-2129 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent E20-E28
Origin http://dx.doi.org/10.1159/000210575
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000265628600003
URI http://repositorio.unifesp.br/handle/11600/31117

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