Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

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

Cuccuini W*, Poitevin S*, Poitevin G, Dignat-George F, Cornillet-Lefebvre P, Sabatier F, Nguyen P. *Equal contribution. 2010, 8/9 (Sept). Journal of Thrombosis and Haemostasis. Pages : 2042-2052. Impac factor : 5.439

RÉFÉRENCES

Abstract

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)-α-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-α. 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-α 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.

http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2010.03936.x/abstract