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DEVELOPMENT OF RODENT MODELS FOR XENOTRANSPLANTATION

异种移植啮齿动物模型的开发

基本信息

批准号：
6394656
负责人：
DONALD V CRAMER
金额：
$ 27.58万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-01 至 2002-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6394656
关键词：
biological models guinea pigs hamsters laboratory mouse laboratory rabbit laboratory rat model design /development transplantation immunology xenotransplantation

项目摘要

This research project is designed to develop relevant, cost effective rodent models for human xenotransplantation. The work outlined in the present proposal is designed to: (1) exchange cardiac xenografts between selected groups of donor/recipient species combinations and establish the immunopathologic characteristics of the type of xenograft reaction observed; (2) establish the nature of the immunoglobulin genes and B cell subsets that control the humoral response to xenografts and whether this response is consistent for different donor species; (3) compare the pattern of rejection for cardiac, liver, kidney, and pancreatic islet xenografts in a single door/recipient species combination, and (4) use rat monoclonal antibodies to isolate and characterize xenograft target antigens, first in hamster and later in related species, to establish the most appropriate species combination for providing the basis for similar experiments in species that may serve as potential xenograft donors for humans. The information derived from these studies will be important for defining which species of small animals can be considered to represent the best models for human pig and/or primate xenografting. The definition of the most appropriate rodent model for human xenotransplantation has the potential for wide use by investigators in many areas of medical research, especially those in which the use of tissues from non-human donors are used as a part of new treatment strategies for diseases such as diabetes, neurological disorders, cardiovascular disease and specific gene therapies.

该研究项目旨在开发相关的、具有成本效益的用于人类异种移植的啮齿动物模型。中概述的工作目前的提案旨在：（1）在之间交换心脏异种移植物选定的供体/受体物种组合组并建立异种移植反应类型的免疫病理学特征观察到； (2) 建立免疫球蛋白基因和B细胞的性质控制对异种移植物的体液反应的子集以及这是否不同供体物种的反应是一致的； (3)比较心脏、肝脏、肾脏和胰岛的排斥反应模式单门/受体物种组合中的异种移植物，以及（4）使用大鼠用于分离和表征异种移植靶点的单克隆抗体抗原，首先在仓鼠中，然后在相关物种中，以建立最合适的物种组合，为类似的研究提供基础在可能作为潜在异种移植供体的物种中进行的实验人类。从这些研究中获得的信息对于定义哪些小动物物种可以被视为代表人猪和/或灵长类动物异种移植的最佳模型。的定义最适合人类异种移植的啮齿动物模型是研究人员在医学研究的许多领域广泛使用的潜力，尤其是那些使用非人类捐赠者的组织的情况用作糖尿病等疾病新治疗策略的一部分，神经系统疾病、心血管疾病和特定基因疗法。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evidence for recipient derived fibroblast recruitment and activation during the development of chronic cardiac allograft rejection.

慢性心脏同种异体移植排斥反应发生过程中受体来源的成纤维细胞募集和激活的证据。

DOI：
10.1097/01.tp.0000066362.37931.6d
发表时间：
2003
期刊：
Transplantation.
影响因子：
0
作者：
Wu,GordonD;Tuan,Tai-Lan;Bowdish,MichaelE;Jin,Yang-Sun;Starnes,VaughnA;Cramer,DonaldV;Barr,MarkL
通讯作者：
Barr,MarkL

Maturation of xenoantibody gene expression during the humoral immune response of rats to hamster xenografts.

大鼠对仓鼠异种移植物的体液免疫反应期间异种抗体基因表达的成熟。

DOI：
10.1034/j.1399-3089.2001.00136.x
发表时间：
2001
期刊：
Xenotransplantation.
影响因子：
0
作者：
Wu,GD;Gochi,E;Jin,YS;Swensson,J;Starnes,VA;Cramer,DV
通讯作者：
Cramer,DV

Vascular endothelial cell apoptosis induced by anti-donor non-MHC antibodies: a possible injury pathway contributing to chronic allograft rejection.

DOI：
10.1016/s1053-2498(02)00457-6
发表时间：
2002-11
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
0
作者：
Gordon D. Wu;Yangsun Jin;Roberto Salazar;W. Dai;N. Barteneva;M. Barr;Lura W Barsky;V. Starnes;D. Cramer
通讯作者：
Gordon D. Wu;Yangsun Jin;Roberto Salazar;W. Dai;N. Barteneva;M. Barr;Lura W Barsky;V. Starnes;D. Cramer

The human antibody response to porcine xenoantigens is encoded by IGHV3-11 and IGHV3-74 IgVH germline progenitors.

针对猪异种抗原的人抗体反应由 IGHV3-11 和 IGHV3-74 IgVH 种系祖细胞编码。