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Endothelial Colony-Forming Cells from Idiopathic Pulmonary Fibrosis Patients Have a High Procoagulant Potential

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive and irreversible lung disease constantly associated with a major vascular remodeling process. Endothelial colony-forming cells (ECFCs) are human vasculogenic cells proposed as a cell therapy product or liquid biopsy in vascular disorders. Since the link between IPF and thrombosis has been largely proposed, the aim of our study was to explore hypercoagulability states in ECFCs from patients with IPF. We performed Thrombin generation assay (TGA) in cord blood (CB)-ECFCs, peripheral blood (PB)-ECFCs and IPF-ECFCs. Endogenous thrombin potential and peak were higher in IPF-ECFCs compared to CB-ECFCs and PB-ECFCs. As thrombin generation in ECFCs was increased, we evaluated anticoagulant proteins expressed on ECFCs membrane and identified thrombomodulin and EPCR. We found a significant decrease of both anticoagulant proteins at membrane using flow cytometry. This study is the first to examine ECFC thrombin generation in IPF. This new finding strongly argues for a role of ECFC in IPF pathophysiology and thrombotic related disorders in IPF.

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Funding

This work was supported by grants of the PROMEX STIFTUNG FUR DIE FORSCHUNG Foundation.

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Authors and Affiliations

  1. Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, AP-HP, Georges Pompidou European Hospital, F-75006 Paris, France, Service d’Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), 75015, Paris, France

    Paul Billoir, Adeline Blandinières, Nicolas Gendron, Aurélien Philippe & David M. Smadja

  2. Normandie Univ, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit, 76000, Rouen, France

    Paul Billoir

  3. Université de Paris, PARCC, INSERM, 75015 Paris, France, AP-HP, Georges Pompidou European Hospital, Service d’accueil des urgences, 75015, Paris, France

    Richard Chocron

  4. Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, AP-HP, Georges Pompidou European Hospital, Service de physiologie respiratoire et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), F-75015, Paris, France

    Sven Gunther

  5. Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, France, Institut Curie, Cytometry Platform, 75006, Paris, France

    Coralie L. Guerin

  6. Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, France, AP-HP, Georges Pompidou European Hospital, Service de pneumologie, 75015, Paris, France

    Dominique Israël-Biet

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  1. Paul Billoir
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  2. Adeline Blandinières
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  9. David M. Smadja
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Correspondence to David M. Smadja.

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Billoir, P., Blandinières, A., Gendron, N. et al. Endothelial Colony-Forming Cells from Idiopathic Pulmonary Fibrosis Patients Have a High Procoagulant Potential. Stem Cell Rev and Rep 17, 694–699 (2021). https://doi.org/10.1007/s12015-020-10043-4

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