Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

文献类型： 外文期刊

第一作者： Ji, Hongchen

作者： Ji, Hongchen;Li, Xiao;Yue, Shuqiang;Zhang, Zhuochao;Ma, Ben;Wang, Jing;Pu, Meng;Wang, Desheng;Duan, Juanli;Tao, Kaishan;Dou, Kefeng;Li, Junjie;Chen, Hui;Zhou, Liang;Feng, Chong;Pan, Dengke

作者机构：

关键词： Xenotransplantation;Tissue factor/Factor VIIa;Tissue factor pathway inhibitor;Animal model;Bone marrow mesenchymal stem cells

期刊名称：CELLULAR PHYSIOLOGY AND BIOCHEMISTRY （ 影响因子：5.5； 五年影响因子：4.354 ）

ISSN： 1015-8987

年卷期： 2015 年 36 卷 1 期

页码：

收录情况： SCI

摘要： Background: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI. Copyright (C) 2015 S. Karger AG, Basel

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