Tissue factor up-regulation in proinflammatory conditions confers thrombin generation capacity to endothelial colony-forming cells without influencing non-coagulant properties in vitro.
Fiche publication
Date publication
septembre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CORNILLET-LEFEBVRE Pascale, Pr NGUYEN Philippe
Tous les auteurs :
Cuccuini W, Poitevin S, Poitevin G, Dignat-George F, Cornillet-Lefebvre P, Sabatier F, Nguyen P
Lien Pubmed
Résumé
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, in terms of thrombogenicity particularly in inflammatory conditions, currently observed in such patients. Tissue factor (TF) can trigger coagulation and may support thrombogenicity. TF is also a key receptor in angiogenesis. OBJECTIVE: The present study was designed to (i) evaluate the capacity of resting and tumour necrosis factor-alpha (TNF)-alpha-stimulated late-outgrowth endothelial colony-forming cells (ECFCs) to express TF and (ii) investigate the effect of TF/FVII(a) interaction on procoagulant and non-procoagulant activities of ECFCs in vitro. METHODS: ECFCs from cord blood (cb) and adult peripheral blood (ab) were analyzed for TF expression and activity using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, Western blot and a thrombin generation assay. Non-procoagulant properties of TF-expressing ECFCs were investigated in vitro using wound-healing, cell proliferation, tube formation and spheroid-based assays. RESULTS: ECFCs expressed TF in response to TNF-alpha. The up-regulation of TF conferred to ECFCs a FVII(a)-dependent thrombin generation activity. Compared with cb-ECFC, ab-ECFCs can display a higher level of constitutive TF expression and activity, with a notable heterogeneity among donors. TF/FVIIa interaction did not modify non-procoagulant properties of TNF-alpha stimulated cb-ECFCs in vitro. CONCLUSIONS: Proinflammatory conditions up-regulate TF expression in ECFCs. This expression confers to ECFCs a strong thrombin generation capacity without influencing their non-coagulant properties. Our results suggest that EPC-based cell therapy may be associated with prothrombotic risk which could be limited by inhibiting TF without affecting the proangiogenic capacity of the cells.
Référence
J Thromb Haemost. 2010 Sep;8(9):2042-52