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Title: Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury
Authors: Wang, Pamella Huey Mei [UNIFESP]
Schwindt, Telma Tiemi [UNIFESP]
Barnabe, Gabriela Filoso [UNIFESP]
Motta, Fabiana Louise Teixeira [UNIFESP]
Semedo, Patricia [UNIFESP]
Beraldo, Felipe Caetano
Mazzali, Marilda
Reis, Marlene Antonia dos
Teixeira, Vicente de Paula Antunes
Pacheco-Silva, Alvaro [UNIFESP]
Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]
Camara, Niels Olsen Saraiva [UNIFESP]
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
Keywords: Neurospheres
Neural precursor cells
Ischemia and reperfusion injury, renal
Issue Date: 1-Jan-2009
Publisher: Karger
Citation: Nephron Experimental Nephrology. Basel: Karger, v. 112, n. 1, p. E20-E28, 2009.
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
ISSN: 1660-2129
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