Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult...

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Main Authors:	Stephenne, Xavier, Nicastro, Emanuele, Eeckhoudt, Stephane, Hermans, Cedric, Nyabi, Omar, Lombard, Catherine, Najimi, Mustapha, Sokal, Etienne
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416788/

id	pubmed-3416788
recordtype	oai_dc
spelling	pubmed-34167882012-08-16 Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity Stephenne, Xavier Nicastro, Emanuele Eeckhoudt, Stephane Hermans, Cedric Nyabi, Omar Lombard, Catherine Najimi, Mustapha Sokal, Etienne Research Article Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs), ii) to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts) or liver origin (liver myofibroblasts), and iii) to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry), we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans. Public Library of Science 2012-08-10 /pmc/articles/PMC3416788/ /pubmed/22900053 http://dx.doi.org/10.1371/journal.pone.0042819 Text en © 2012 Stephenne et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Stephenne, Xavier Nicastro, Emanuele Eeckhoudt, Stephane Hermans, Cedric Nyabi, Omar Lombard, Catherine Najimi, Mustapha Sokal, Etienne
spellingShingle	Stephenne, Xavier Nicastro, Emanuele Eeckhoudt, Stephane Hermans, Cedric Nyabi, Omar Lombard, Catherine Najimi, Mustapha Sokal, Etienne Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
author_facet	Stephenne, Xavier Nicastro, Emanuele Eeckhoudt, Stephane Hermans, Cedric Nyabi, Omar Lombard, Catherine Najimi, Mustapha Sokal, Etienne
author_sort	Stephenne, Xavier
title	Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
title_short	Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
title_full	Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
title_fullStr	Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
title_full_unstemmed	Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
title_sort	bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity
description	Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs), ii) to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts) or liver origin (liver myofibroblasts), and iii) to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry), we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416788/
_version_	1611549055563857920

Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

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