PREVENTION OF HYPERACUTE REJECTION IN AN EX-VIVO PIG TO HUMAN CARDIAC XENOGRAFT

预防离体猪对人心脏异种移植物的超急性排斥反应

• 批准号: 6275297
• 负责人: Jonathan P Fryer
• 金额: $ 2.26万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6275297
• 关键词: binding proteins; cardiovascular transplantation; complement pathway; disease /disorder prevention /control; human tissue; perfusion; swine; synthetic peptide; transplant rejection; xenotransplantation

Because of the severe shortage of available human organs for donation, other species have been considered as potential donors for human transplantation. Of the options available, the pig appears to be the most suitable candidate. Hyperacute rejection has been a major barrier to pig- to-human transplantation, although several strategies have been successful in preventing this. Despite preventing hyperacute rejection, delayed xenografic rejection occurs which is characterized by endothelial cell activation and invasion of macrophages and natural killer cells. Although many of the successful strategies to avert hyperacute rejection have used approaches which prevent complete activation of the complement cascade, none have attempted to inhibit the complement cascade in its earliest phases. Deposition of the initial components of the complement cascade (C1, C4, C2) can lead to the accumulation of inflammatory cells and may contribute to endothelial cell activation thus creating a situation which is consistent with delayed xenograft rejection. Using novel synthetic peptides (complementary binding peptides) developed at Northwestern University, we will attempt to block the deposition of the early components of the complement cascade, thus preventing hyperacute rejection as well as the pro-inflammatory stimulus which is elicited from these early components. This will be tested in an ex vivo perfusion circuit where human blood is perfused through a pig heart with and without the complementary binding peptides.

由于可供捐献的人体器官严重短缺， 其他物种被认为是人类的潜在捐助者 移植。在可用的选项中，猪似乎是最多的 合适的候选人。超急性排斥反应一直是猪的主要障碍 人体移植，尽管有几种策略已经成功 为了防止这种情况发生。尽管可以防止超急性排斥反应，但延迟 发生异种排斥，其特征是内皮细胞 巨噬细胞和自然杀伤细胞的激活和侵袭。虽然 许多避免超急性排斥反应的成功策略已被使用 阻止补体级联完全激活的方法， 没有人试图在最早的时候抑制补体级联反应 阶段。补体级联初始成分的沉积 （C1、C4、C2）可导致炎症细胞积聚，并可能 有助于内皮细胞活化，从而创造了一种情况 与迟发性异种移植排斥反应一致。使用新型合成 西北大学开发的肽（互补结合肽） 大学，我们将尝试阻止早期成分的沉积 补体级联反应，从而防止超急性排斥反应 促炎刺激是由这些早期的 成分。这将在离体灌注回路中进行测试，其中 人的血液通过猪心脏灌注，有或没有 互补结合肽。