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: Xavier Stephenne, Emanuele Nicastro, Stephane Eeckhoudt, Cedric Hermans, Omar Nyabi, Catherine Lombard, Mustapha Najimi, Etienne Sokal
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3416788?pdf=render
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author Xavier Stephenne
Emanuele Nicastro
Stephane Eeckhoudt
Cedric Hermans
Omar Nyabi
Catherine Lombard
Mustapha Najimi
Etienne Sokal
author_facet Xavier Stephenne
Emanuele Nicastro
Stephane Eeckhoudt
Cedric Hermans
Omar Nyabi
Catherine Lombard
Mustapha Najimi
Etienne Sokal
author_sort Xavier Stephenne
collection DOAJ
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.
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spelling doaj.art-7fb73d4fcf694ddd8fd4acd4c3691a9c2022-12-22T00:25:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4281910.1371/journal.pone.0042819Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity.Xavier StephenneEmanuele NicastroStephane EeckhoudtCedric HermansOmar NyabiCatherine LombardMustapha NajimiEtienne SokalIslet 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.http://europepmc.org/articles/PMC3416788?pdf=render
spellingShingle Xavier Stephenne
Emanuele Nicastro
Stephane Eeckhoudt
Cedric Hermans
Omar Nyabi
Catherine Lombard
Mustapha Najimi
Etienne Sokal
Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity.
PLoS ONE
title 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_short Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity.
title_sort bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity
url http://europepmc.org/articles/PMC3416788?pdf=render
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