Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

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Mei Wang, Pamella Huey ^[1] ; Schwindt, Telma T. ^[2] ; Barnabe, Gabriela Filoso ^[2] ; Motta, Fabiana L. T. ^[2] ; Semedo, Patricia ^[1] ; Beraldo, Felipe Caetano ^[3] ; Mazzali, Marilda ^[3] ; dos Reis, Marlene Antonia ^[4] ; Antunes Teixeira, Vicente de Paula ^[4] ; Pacheco-Silva, Alvaro ^{[5, 1]} ; de Mello, Luis Eugenio A. ^[2] ; Camara, Niels O. S. ^{[1, 6]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Lab Imunol Clin & Expt, Div Nephrol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Neurophysiol Lab, Div Physiol, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Div Nephrol, Campinas, SP - Brazil

^[4] Univ Fed Triangulo Mineiro, Div Pathol, Belo Horizonte, MG - Brazil

^[5] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Lab Transplantat Immunobiol, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEPHRON EXPERIMENTAL NEPHROLOGY; v. 112, n. 1, p. E20-E28, 2009.
• Citações Web of Science: 7

Resumo

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 (AU)

• Processo FAPESP: 04/13826-5 - Contribuição ao aumento da sobrevida do enxerto em transplante de rim: papel dos mecanismos imunológicos e não imunológicos na fisiopatogenia da insuficiência renal aguda
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 04/08311-6 - Mecanismos moleculares, celulares e fisiopatológicos da insuficiência renal aguda
• Beneficiário: Nestor Schor
• Modalidade de apoio: Auxílio à Pesquisa - Temático