随着GTKO 小型猪和转hCPRP 基因猪的问世，由α-1,3-半乳糖抗原和天然抗体引发的异种超急性排斥反应已得到有效控制，但因猪与灵长类动物的凝血-抗凝系统不相容引发的受体凝血功能紊乱，介导了迟发性免疫排斥反应的发生，阻碍移植物的长期存活。目前发现猪源AT-Ⅲ和TFPI 不能在人体内发挥抗凝作用，致使移植物血管内产生广泛微血栓，并继发消耗性凝血障碍，最终导致移植物失活和受体死亡。针对此问题，本课题拟以GTKO.小型猪为供体，恒河猴为受体，建立异种肝移植模型，并采用脂质体法将hAT-Ⅲ和hTFPI.基因导入供体MSC，于术前、术中及术后输入受体体内，观察受体存活时间、免疫排斥发生.率和凝血功能，探讨hAT-Ⅲ和hTFPI 对纠正受体凝血功能紊乱和抑制免疫排斥的作用。本课题的研究，将首次检测hAT-Ⅲ和hTFPI 在异种大器官移植中的应用价值，并为突破人和猪的凝血-抗凝系统不相容。

With the development of GTKO pig and hCPRP transgenic pig, the hyperacute xenograft response caused by α-1,3-galactose and natural antibody can be efficiently control. But the coagulation dysfunction caused by the coagulation and anticoagulation system incompatibility between the pig and primate causes chronic rejection and reduce the survival time of the grafts. Now evidences have been found that porcine antithrombin-III (AT-III) and tissue factor pathway inhibitor (TFPI) cannot play their roles in human body, which cause the formation of microthrombin, consumptive coagulopathy and finally cause the deaths of grafts and recipient. To solve this problem, we plan to make a transplantation models with pig (as the donor) and monkey (as the recipient) and transfer the human AT-III and human TFPI to the donor MSC and inject the transgenic MSC to the recipient. We plan to observe the survival time, immune response and the coagulation function. In this way, we can find the function of hAT-III and hTFPI in correcting coagulation dysfunction and controlling immune rejection. Our subject will first examine the use of hAT-III and hTFPI in big organ xenotransplantation and make outbreaking progress for the coagulation and anticoagulation incompatibility before the clinical application of xenotransplantation.