当前位置: X-MOL 学术Transpl. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Aspects of histocompatibility testing in xenotransplantation
Transplant Immunology ( IF 1.5 ) Pub Date : 2021-05-17 , DOI: 10.1016/j.trim.2021.101409
Joseph M Ladowski 1 , Julie Houp 2 , Vera Hauptfeld-Dolejsek 2 , Mariyam Javed 1 , Hidetaka Hara 1 , David K C Cooper 1
Affiliation  

Xenotransplantation, using genetically-modified pigs for clinical organ transplantation, is a solution to the organ shortage. The biggest barrier to clinical implementation is the antigenicity of pig cells. Humans possess preformed antibody to pig cells that initiate antibody-mediated rejection of pig organs in primates. Advances in genetic engineering have led to the development of a pig lacking the three known glycan xenoantigens (triple-knockout [TKO] pigs). A significant number of human sera demonstrate no antibody binding to TKO pig cells. As a result of the TKO pig's low antigen expression, survival of life-supporting pig organs in immunosuppressed nonhuman primates has significantly increased, and hope has been renewed for clinical trials of xenotransplantation.

It is important to understand the context in which xenotransplantation's predecessor, allotransplantation, has been successful, and the steps needed for the success of xenotransplantation. Successful allotransplantation has been based on two main immunological approaches – (i) adequate immunosuppressive therapy, and (ii) careful histocompatibility matching. In vivo studies suggest that the available immunosuppressive regimens are adequate to suppress the human anti-pig cellular response. Methods to evaluate and screen patients for the first clinical xenotransplantation trial are the next challenge. The goal of this review is to summarize the history of histocompatibility testing, and the available tools that can be utilized to determine xenograft histocompatibility.



中文翻译:

异种移植中组织相容性测试的各个方面

异种移植,使用转基因猪进行临床器官移植,是解决器官短缺的一种方法。临床实施的最大障碍是猪细胞的抗原性。人类拥有针对猪细胞的预先形成的抗体,这些抗体会引发抗体介导的对灵长类动物器官的排斥。基因工程的进步导致开发出缺乏三种已知聚糖异种抗原的猪(三重敲除 [TKO] 猪)。大量人血清显示没有抗体与 TKO 猪细胞结合。由于 TKO 猪的低抗原表达,免疫抑制的非人灵长类动物维持生命的猪器官的存活率显着提高,异种移植临床试验的希望重新燃起。

了解异种移植的前身同种异体移植成功的背景以及异种移植成功所需的步骤非常重要。成功的同种异体移植基于两种主要的免疫学方法——(i) 充分的免疫抑制治疗,和 (ii) 仔细的组织相容性匹配。体内研究表明,现有的免疫抑制方案足以抑制人类抗猪细胞反应。为首次临床异种移植试验评估和筛选患者的方法是下一个挑战。本综述的目的是总结组织相容性测试的历史,以及可用于确定异种移植组织相容性的可用工具。

更新日期:2021-05-22
down
wechat
bug