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Hepatic endothelial cell function in the assessment of graft viability after liver transplantation and modification of donor MHC antigens by antisense gene transfer to prevent rejection of transplanted organs

肝内皮细胞在肝移植后移植物活力评估中的功能以及通过反义基因转移修饰供体 MHC 抗原以防止移植器官排斥

基本信息

批准号：
08671411
负责人：
SHIMIZU Hiroaki
金额：
$ 1.41万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

1.In our first study, we investigated the mechanism of cold ischemia-reperfusion injury, especially the relationship between sinusoidal endothelial cell (SEC) function and graft viability after liver transplantation. According our results, graft failure after cold ischemia-reperfusion primarily resulted from SEC damage, leading to decreased sinusoidal blood flow. Hepatocellular ischemic necrosis might occur secondarily as a result of decreased portal reflow, with eventual graft failure. Therefore, monitoring serum hyaluronic acid for the assessment of SEC function, and hepatic venous oxygen saturation levels for evaluation of hepatic microcirculation after reperfusion might be useful to estimate the prognosis of a graft after liver transplantation.2.In our second study, we examined whether insertion of an antisense vector into the allograft could down-regulate the expression of the target antigens and to prevent the rejection of transplanted organs. In vitro study, down-regulation of donor MHC class I antigen expression on the donor cells was observed after transfection of plasmid vector containing antisense of donor target antigen in vitro and also immunological response to these cells. However, in vivo, efficient transfection of antisense DNA to the donor graft organ was very difficult at present. Now we are developing new technology to provide for efficient in vivo transfection.

1.本研究首先探讨了肝移植术后冷缺血再灌注损伤的机制，特别是肝窦内皮细胞（SEC）功能与移植物存活的关系。根据我们的研究结果，冷缺血再灌注后移植物衰竭主要是由于SEC损伤，导致窦状隙血流减少。肝细胞缺血性坏死可能继发于门静脉回流减少，最终导致移植物衰竭。因此，监测血清透明质酸以评估SEC功能，监测肝静脉血氧饱和度水平以评估再灌注后肝脏微循环可能有助于评估肝移植术后的预后。我们检测了在同种异体移植物中插入反义载体是否可以降低-调节靶抗原的表达并防止移植器官的排斥反应。体外实验中，供体靶抗原反义核酸质粒载体转染供体细胞后，供体细胞MHC Ⅰ类抗原表达下调，并观察到供体细胞产生的免疫应答。然而，目前在体内，将反义DNA有效地转染到供体移植器官中是非常困难的。现在，我们正在开发新的技术，以提供有效的体内转染。