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，其他物种被认为是潜在的人体移植供体。在可用的选项中，猪似乎是最合适的候选人。超急性排斥反应一直是猪到人移植的主要障碍，尽管有几种策略已经成功地防止了这种情况。尽管可以预防超急性排斥反应，但延迟异种排斥反应的发生以内皮细胞活化和巨噬细胞和自然杀伤细胞的侵袭为特征。尽管许多成功的避免超急性排斥反应的策略都使用了阻止补体级联完全激活的方法，但没有人试图在其早期阶段抑制补体级联。补体级联初始组分（C1, C4, C2）的沉积可导致炎症细胞的积累，并可能促进内皮细胞的激活，从而产生与延迟异种移植排斥反应一致的情况。利用西北大学开发的新型合成肽（互补结合肽），我们将尝试阻断补体级联早期成分的沉积，从而防止超急性排斥反应以及由这些早期成分引起的促炎刺激。这将在体外灌注回路中进行测试，其中人类血液通过猪心脏灌注，并在有无补充结合肽的情况下进行灌注。

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.