ORTHOTOPIC LIVER TRANSPLANTATION

原位肝移植

• 批准号: 6475284
• 负责人: THOMAS E STARZL
• 金额: $ 13.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-01-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6475284
• 关键词: artificial immunosuppression; baboons; cytokine; dendritic cells; dogs; guinea pigs; hamsters; hematopoietic stem cells; hepatocyte growth factor; immune tolerance /unresponsiveness; inhibitor /antagonist; laboratory mouse; laboratory rat; liver transplantation; phosphatidate; tissue mosaicism; transplant rejection; xenotransplantation

This application is designed to study the mechanisms of transplantation tolerance with particular reference to the liver. The principal hypothesis driving these studies if the Principal Investigator's so- called "Two-Way Paradigm". This proposes that the ultimate outcome of allograft transplantation represents the composite of two immunologic forces: classic host vs. graft attack, i.e. allograft rejection, and graft vs. host. The latter is an occult immunologic force at work. Although the clinical entity of graft vs. host disease in liver transplantation is uncommon, it represents in essence a serious effort by leukocytes contained in the graft to reject the recipient after their migration. Thus, it is the investigator's proposal that the recipient becomes populated with small numbers of cells from the donor organ and that the effect of this "graft vs. host" reaction is the promotion of tolerance. As these cells leave the graft, they are replaced in the transplant by immune cells of the recipient in successful cases. In this hypothesis, host vs. graft disease if uncontrolled is bad because it leads to rejection of the allograft. The other way round, graft vs. host disease if unchecked can kill the patient, but if controlled it tempers rejection. The studies proposed will test this hypothesis. Moreover, the investigators will attempt to develop novel techniques to modify the number and character of the donor cells that ultimately reside in the recipient and promote tolerance to the allograft.

此应用程序旨在研究移植的机制 耐受性，特别是肝脏。 校长 假设驱动这些研究，如果主要研究者是如此- 叫做“双向范式”这意味着，最终的结果 同种异体移植代表了两种免疫学 作用力：经典宿主vs.移植物攻击，即同种异体移植物排斥，以及 移植物抗宿主 后者是一种神秘的免疫力在起作用。 虽然肝脏移植物抗宿主病的临床实体 移植是不常见的，它本质上代表了一种严肃的努力， 移植物中含有的白细胞在移植后排斥受体， 迁移 因此，研究人员建议， 从捐赠器官中获得少量细胞， 这种“移植物抗宿主”反应的效果是促进 宽容 当这些细胞离开移植物时， 在成功的情况下，通过接受者的免疫细胞进行移植。 在这 假设，宿主与移植物疾病如果不受控制是不好的，因为它 导致同种异体移植物的排斥反应。 反之，移植物抗宿主 这种疾病如果不加以控制，会使病人死亡，但如果加以控制， 排斥反应 拟议的研究将检验这一假设。 此外，委员会认为， 研究人员将尝试开发新的技术来改变 最终驻留在细胞中的供体细胞的数量和特征 并促进对同种异体移植物的耐受性。

项目成果

Orthotopic liver transplantation in the mouse.

• DOI: 10.1097/00007890-199109000-00039
• 发表时间: 1991-09
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: S. Qian;J. Fung;A. Demetris;S. Ildstad;T. Starzl

Tacrolimus (FK506)-Associated Renal Pathology.

• DOI: 10.1097/00125480-199707000-00032
• 发表时间: 1997-07-01
• 期刊: Advances in anatomic pathology
• 影响因子: 6.7
• 作者: Randhawa, Parmjeet S;Starzl, Thomas E;Demetris, Anthony Jake
• 通讯作者: Demetris, Anthony Jake

Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells.

• DOI: 10.1097/00007890-199408270-00015
• 发表时间: 1994-08
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: J. Woo;Lina L. Lu;A. Rao;Youping Li;V. Subbotin;T. Starzl;A. Thomson

Mouse liver transplantation tolerance: the role of hepatocytes and nonparenchymal cells.

• 发表时间: 1995
• 期刊: Transplantation proceedings
• 影响因子: 0.9
• 作者: N. Thai;S. Qian;F. Fu;Y. Li;H. Sun;A. Demetris;R. Duquesnoy;T. Starzl;J. Fung

Overview of FK 506 in transplantation

FK 506 在移植中的概述

• 发表时间: 1992
• 作者: J. Fung;K. Abu;Todo;Ronald Shapiro;A. Tzakis;Mark Jordan;John Armitage;A. Jain;M. Alessiani;Maureen Martin;O. Bronster;A. Stieber;Robert L. Kormos;Robert R. Selby;Robert D. Gordon;D. Przepiorka;Elana J. Bloom;T. Starzl
• 通讯作者: T. Starzl