间充质干细胞
组织因子
移植
凝血酶
药理学
抗凝血酶
凝结
免疫学
化学
医学
癌症研究
生物
细胞生物学
肝素
血小板
内科学
作者
Xavier Stéphenne,Emanuele Nicastro,Stéphane Eeckhoudt,Cédric Hermans,Omar Nyabi,Catherine Lombard,Mustapha Najimi,Étienne Sokal
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2012-08-10
卷期号:7 (8): e42819-e42819
被引量:49
标识
DOI:10.1371/journal.pone.0042819
摘要
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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