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Generation of human inflammation-resistant endothelial progenitor cells by A20 gene transfer

Dunoyer-Geindre, Sylvie
Blot-Chabaud, Marcel
Sabatier, Florence
Dignat-George, Francoise
Published in Journal of vascular research. 2010, vol. 47, no. 2, p. 157-167
Abstract Inflammatory activation of the vascular endothelium is a major contributory factor to ischemic cardiovascular disease. Endothelial progenitor cells (EPCs) are being investigated for the treatment of ischemic disease or to coat vein grafts for bypass surgery. As an inflammatory environment might reduce their therapeutic efficacy, we sought to generate EPCs that are less sensitive to inflammatory activation. EPCs were obtained from human umbilical cord blood and transduced with a lentiviral vector for stable expression of A20, an anti-inflammatory protein. Nontransduced and green-fluorescent-protein-transduced cells were used as controls. Expression of A20 by EPCs did not modify cell morphology or expression of a panel of 20 proteins known to contribute to angiogenesis. Also, A20 had no effect on the capacity of EPCs to form tube-like structures in Matrigel. A20 expression reduced EPC activation by tumor necrosis factor-alpha and interleukin-1beta as determined from changes in vascular cell adhesion molecule 1 and E-selectin expression and decreased monocyte transmigration through a monolayer of EPCs. In conclusion, EPCs can be genetically modified to overexpress A20 in a stable fashion. These cells become less sensitive to inflammatory stimuli. This may be of interest in cell-based therapeutic approaches for clinical settings where inflammation is an important pathogenic factor.
Keywords Angiogenic Proteins/geneticsCells, CulturedCulture Media, Conditioned/metabolismE-Selectin/genetics/metabolismEndothelial Cells/*immunologyFetal Blood/cytology/immunologyFetal Stem Cells/*immunologyGene Expression RegulationGenetic VectorsHumansInflammation/genetics/immunology/*prevention & controlInflammation Mediators/metabolismInterleukin-1beta/metabolismIntracellular Signaling Peptides and Proteins/geneticsLentivirus/geneticsLeukocyte RollingMonocytes/immunologyNeovascularization, Physiologic/geneticsNuclear Proteins/*biosynthesis/geneticsRNA, Messenger/metabolism*Transduction, GeneticTumor Necrosis Factor-alpha/metabolismVascular Cell Adhesion Molecule-1/genetics/metabolism
PMID: 19851077
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Research groups Endothélium vasculaire (11)
Geneva Platelet Group (13)
La maladie thromboembolique veineuse (808)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
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LIU, Jia Wei et al. Generation of human inflammation-resistant endothelial progenitor cells by A20 gene transfer. In: Journal of vascular research, 2010, vol. 47, n° 2, p. 157-167. doi: 10.1159/000250094 https://archive-ouverte.unige.ch/unige:21087

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Deposited on : 2012-05-23

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