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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Anticuerpos monoclonales > DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista >

Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells
Authors: Fernandez-Ruiz, V. (Verónica)
Kawa, M. (Milosz)
Berasain, C. (Carmen)
Iñiguez, M. (María)
Schmitz, V. (Volker)
Martinez-Anso, E. (Eduardo)
Iñarrairaegui, M. (Mercedes)
Herrero, J.I. (José Ignacio)
Sangro, B. (Bruno)
D'Avola, D. (Delia)
Quiroga, J. (Jorge)
Qian, C. (Cheng)
Prieto, J. (Jesús)
Keywords: Endothelial Cells/cytology
Gene Therapy/methods
Liver Failure, Acute/therapy
Organic Cation Transport Proteins/genetics
Stem Cell Transplantation/methods
Stem Cells/physiology
Issue Date: 2011
Publisher: Elsevier
Publisher version: http://dx.doi.org/10.1016/j.jhep.2011.01.036
ISSN: 0168-8278
Citation: Fernandez-Ruiz V, Kawa M, Berasain C, Iñiguez M, Schmitz V, Martinez-Anso E, et al. Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells. J Hepatol 2011 Oct;55(4):828-837.
Abstract
BACKGROUND & AIMS: Cell therapy has been used to attenuate liver injury. Here we evaluated whether genetic engineering of either bone marrow-derived mononuclear cells (MNC) or endothelial progenitor cells (EPC) many enhance their hepatoprotective properties. METHODS: Mice with ConA-induced hepatitis or with lethal fulminant hepatitis resulting from administration of an adenovirus encoding CD40L (AdCD40L) received an intra-splenic injection of saline or 2 × 10(6) unmodified MNC or EPC or the same cells transduced ex vivo with an adenovirus expressing luciferase (MNCLUC and EPCLUC) or encoding the hepatoprotective cytokine cardiotrophin-1 (CT-1) (MNCCT-1 and EPCCT-1). We analyzed the extent of liver damage, the intensity of inflammatory reaction, and animal survival. RESULTS: Luciferase immunohistochemistry showed that after injection into the spleen, the engineered cells migrated efficiently to the damaged liver. In mice with ConA hepatitis EPCCT-1, but not other forms of cell therapy, significantly decreased serum transaminases and induced more intense histological improvement than other treatments. This superior therapeutic effect was associated with upregulation of cytoprotective molecules including IGF-I and EGF, lower expression of proinflammatory cytokines, IL-1b and TNFα, and decreased granzyme B levels. In AdCD40L-induced lethal fulminant hepatitis, EPCCT-1 also exceeded other cell therapies in attenuating the expression of proinflammatory mediators and hepatic injury enabling 35.7% survival while mortality was 100% in the other treatment groups. CONCLUSIONS: Genetic engineering of EPC to overexpress CT-1 enhances the hepatoprotective properties of EPC and constitutes a therapy that deserves consideration for acute liver failure. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Permanent link: http://hdl.handle.net/10171/20301
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista

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