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

由于可供捐赠的人体器官严重短缺， 其他物种被认为是人类的潜在捐赠者 移植。在可选的选项中，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- 人与人之间的移植，尽管有几种策略已经成功 来阻止这种情况发生。尽管预防了超急性排斥反应，但延迟了 以内皮细胞为特征的异种排斥反应的发生 巨噬细胞和自然杀伤细胞的激活和入侵。虽然 许多成功的避免超急性排斥反应的策略已经使用 防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的级联 阶段。补体级联的初始成分的沉积 (C1、C4、C2)可导致炎症细胞积聚，并可能 有助于内皮细胞的激活，从而创造出一种 符合延迟性异种移植排斥反应。使用新型合成材料 西北大学开发的多肽(互补结合多肽) 大学，我们将试图阻止沉积早期的成分 补体级联，从而防止超急性排斥反应以及 从这些早期引发的促炎刺激 组件。这将在体外灌流电路中进行测试， 人血在猪的心脏中灌流，有和没有 互补结合多肽。

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.