Study of Xenotransplatation Using Gene Engineering Technique

在异种器官移植中，由天然抗体、异种抗原和补体诱导的超急性排斥反应在再灌注后几分钟或几小时内发生。本研究在体外研究补体调节因子（HRF 20和RRF 20）双转基因对异种细胞抑制补体依赖性细胞毒性作用的基础上，建立了HRF 20和RRF 20双转基因小鼠，并采用脾细胞注射模型分析了异种抗体产生的机制。在异种脾细胞注射中，与同种和同种脾细胞注射模型相比，脾中白色髓的边缘区与异种抗体的增加成比例地扩大。抗DNA药物如环磷酰胺可有效抑制异种抗体的产生，蒽环类药物有可能成为临床异种移植免疫抑制剂。因此，异种器官的基因工程和免疫抑制剂的应用是异种器官移植成功的必要条件。

In organ xenotransplantation, hyperacute rejection, induced by natural antibody, xenoantigen, and complement, occurs in a few minutes or hours after reperfusion. In this study, based on the in vitro study, in which the double transduction of complement regulatory factors (DAF and HRF20) is more effective than the single transduction on the xenogeneic cells to inhibit complement-dependent cytotoxicity, double transgenic mice with DAF and HRF20 genes were established.The mechanism of xenoantibody production was analyzed using splenocyte injection model. In xeno-splenocyte injection, marzinal zone of white pulp in the spleen expanded in proportion to the increase of xenoantibody compared to allo- and iso-splenocyte injection models. It was demonstrated that anti-DNA drugs such as Cyclophophamide was useful for the suppresion of xenoantibody production, and anthracycline had a posssible immunosuppressive agent for the clinical xenotransplantation. Thus it is concluded that the gene engineering of xenogenic organs with complemet regulatory factor genes and the use of immunosuppressive drugs are neccesary for the successful clinical xenotransplantation.