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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.
Tissue factor up-regulation in proinflammatory conditions confers thrombin generation capacity to endothelial colony-forming cells without influencing non-coagulant properties in vitro.
- Source :
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Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2010 Sep; Vol. 8 (9), pp. 2042-52. - Publication Year :
- 2010
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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.<br />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.<br />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.<br />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.<br />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.<br /> (© 2010 International Society on Thrombosis and Haemostasis.)
- Subjects :
- Blotting, Western
Cell Proliferation
Coagulants chemistry
Factor VII metabolism
Fetal Blood cytology
Flow Cytometry methods
Humans
Inflammation
Risk
Thrombosis
Tumor Necrosis Factor-alpha metabolism
Wound Healing
Endothelium, Vascular cytology
Thrombin metabolism
Thromboplastin metabolism
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7836
- Volume :
- 8
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 20546120
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2010.03936.x