Tissue factor up-regulation in proinflammatory conditions confers thrombin generation capacity to endothelial colony-forming cells without influencing non-coagulant properties in vitro.

作者: W. CUCCUINI , S. POITEVIN , G. POITEVIN , F. DIGNAT-GEORGE , P. CORNILLET-LEFEBVRE

DOI: 10.1111/J.1538-7836.2010.03936.X

关键词: ThrombinCancer researchTissue factorCell therapyBiologyProinflammatory cytokineAngiogenesisTube formationProgenitor cellVasculogenesisImmunology

摘要: Summary. Background: Endothelial progenitor cells (EPC) are good candidates for cell-based therapy in cardiovascular diseases. However, concerns have been raised about the potential risks of EPC-based cell therapy, terms thrombogenicity particularly inflammatory conditions, currently observed such patients. Tissue factor (TF) can trigger coagulation and may support thrombogenicity. TF is also a key receptor angiogenesis. Objective: The present study was designed to (i) evaluate capacity resting tumour necrosis factor-alpha (TNF)-α-stimulated late-outgrowth endothelial colony-forming (ECFCs) express (ii) investigate effect TF/FVII(a) interaction on procoagulant non-procoagulant activities ECFCs vitro. Methods: from cord blood (cb) adult peripheral (ab) were analyzed expression activity using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, Western blot thrombin generation assay. Non-procoagulant properties TF-expressing investigated vitro wound-healing, proliferation, tube formation spheroid-based assays. Results: ECFCs expressed response TNF-α. The up-regulation conferred FVII(a)-dependent activity. Compared with cb-ECFC, ab-ECFCs display higher level constitutive activity, notable heterogeneity among donors. TF/FVIIa did not modify TNF-α stimulated cb-ECFCs Conclusions: Proinflammatory conditions up-regulate ECFCs. This confers strong without influencing their non-coagulant properties. Our results suggest that be associated prothrombotic risk which could limited by inhibiting affecting proangiogenic cells.

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