Study for Clinical Application of Liver Transplantation

肝移植临床应用研究

• 批准号: 06304035
• 负责人: DOHI Kiyohiko
• 金额: $ 17.92万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06304035/
• 关键词: Liver transplantation; Organ preservation; Non-heart-beating donor; Ischemia; reperfusion injury; Network for organ transplantation; Living-related liver transplantation; Immuno-regulation; Xenotransplantation; 虚血再灌流障害; 脳死ドナー; 再灌流障害; 免疫寛容; 抗接

1.Organ procurement and organ preservation : In the study regarding the relevance of donor nutritional state to graft liver function, it has been demonstrates that poor nutrition of donor caused the endotherial damage of liver sinusoids and results in the impediment to ability of mitochondrial ATP synthesis rates (Satomi and Tanaka). In the study regarding the organ harvesting, the effect of donor hypothermic therapy on graft function and the proper flow rate of initial flushing of graft organs were investigated (Taira). As an useful graft liver viability assays, hepatic protein synthesis rate assay using the graft tissues obtained by needle biopsy and graft effuent assay were developed (Isono and Sugimachi). For taking measures against ischemic damage of graft liver from non-heart beating donor, the novel methods such as the core cooling technique were investigated (Uchino, Satomi and Fukao).2.Indication of liver transplantation : The objective criterions of indication and emergency l … More evel for liver transplantation were described for trial (0ta). For the development of proper registration program for liver transplantation recipients, the detailed follow-up-study of the registered recipientswas done (Sugimachi). A predictive equation for non-A,non-B acute hepatitis was developed for the criterion of indication for liver transplantation (Tanigawa).3.Postoperative management for liver transplantation : The effect of graft liver size-matching on the postoperative graft function and the problem concerning FK506 immunosuppressive therapy in clinical living-related liver transplantation were researched (Yamaoka). As a novel development of immunosuppressive therapy, the drug-delivery modification for the conventional immunosuppressants (intraportal and intra-hepatic-arterial administration of FK506), the induction of immuno-hyporeactivity utilizing donor-antigen infusion (MMC-treated donor splenocyts infusion), the immuno-regulation by use of gene-therapy (CTLA-Ig gene transduction using adenovirus vector), the use of a novel immunosuppressant (Bactobolamine) were researched (Dohi, Monden, Takagi and Tomikawa).4.Study of xenotransplantation : In order to develop the immuno-regulation method in concordant xenotransplantation, the effects of donor bone marrow utilization and the modification of donor antigen with MMC-treatment were investigated (Dohi and Monden). For the purpose of preventing hyperacute rejection in discordant xenotransplantation, human complement regulating genes were successfully transduced in pigs by use of retrovirus vector (Takagi). Less

1.器官获取与器官保存：在有关供者营养状态与移植肝功能相关性的研究中，已有研究表明供者营养不良导致肝窦内源性损害，导致线粒体ATP合成能力受阻(Satomi和Tanaka)。在器官采集的研究中，研究了供体低温治疗对移植器官功能的影响以及移植器官初始冲洗的适宜流量(Taira)。作为一种有用的移植肝存活率测定方法，应用针吸活检和移植物流出液法获得的移植肝组织的蛋白质合成率测定(Isono和Sugimachi)得到了发展。为了预防非心脏跳动中供者移植肝的缺血性损伤，研究了核心冷却技术(Uchino、Satomi和Fukao)等新方法。2.肝移植适应证和急诊L…的客观标准更多的肝移植水平被描述为试验(0TA)。为了制定适当的肝移植受者登记程序，对登记受者进行了详细的随访研究(Sugimachi)。建立了非甲、非乙型急性肝炎的预测方程，作为肝移植适应证的标准(Tanigawa)。3.肝移植的术后管理：研究了供肝大小匹配对术后移植功能的影响以及临床活体肝移植中FK506免疫抑制治疗的问题(Yamaoka)。作为免疫抑制治疗的新进展，对常规免疫抑制剂(门静脉和肝动脉内注射FK506)的药物递送改进，利用供体抗原输注诱导免疫低反应(MMC处理的供体脾细胞输注)，通过基因治疗(腺病毒载体转导CTLA-Ig基因)进行免疫调节，以及新型免疫抑制剂(巴托波拉明)的使用(Dohi，Monden，Takagi和Tomikawa)进行了研究。4.异种移植的研究：为了建立一致性异种移植的免疫调节方法，研究了供体骨髓利用率和供体抗原经MMC处理后的影响(Dohi和Monden)。为了预防非协调性异种移植的超急性排斥反应，利用逆转录病毒载体(Takagi)成功地在猪体内转导了人补体调节基因。较少

项目成果

Sakamoto K.: "Utilization of Organ Preservation Machine as an EX Vivo Swine Liver Perfusion System With Human Whole Blood at 37°C." Transplantation Proceedings. 28. 1919-1920 (1996)

Sakamoto K.：“利用器官保存机作为 37°C 人类全血体外猪肝灌注系统。”1919-1920 年第 28 期（1996 年）

Kamachi H.: "Study of liver function in a graft suffering from warm ischemia in porcine liver transplantaion." Transplantation Proceedings. 28. 1789-1791 (1996)

Kamachi H.：“猪肝移植中遭受热缺血的移植物的肝功能研究。”

Sakamoto K.: "Utilization of Organ Pressrvation Machine as an EX Vivo Swine Liver Perfusion System With Human Whole Blood at 30ﾟC." Transplantation Proceedings. 28. 1919-1920 (1996)

Sakamoto K.：“利用器官加压机作为 30°C 人类全血体外猪肝灌注系统。”28. 1919-1920 (1996)

Gotoh M.: "Role of adhesion molecules in islet allo-and xenograft rejection." Transplantation Proceedings. 28(2). 617- (1996)

Gotoh M.：“粘附分子在胰岛同种异体和异种移植排斥中的作用。”

塚本茂樹: "心停止ドナーにおける肝グラフトコンディショニングの試み。" Organ Biology. 2. 57-63 (1995)

Shigeki Tsukamoto：“心脏骤停捐献者肝脏移植调理的尝试”2. 57-63 (1995)。