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供体。 移植在现有的选择中，猪似乎是最 合适的人选超急性排斥反应一直是猪- 尽管有几种策略已经成功， 来阻止这一切尽管预防了超急性排斥反应， 发生异种移植排斥反应，其特征在于内皮细胞 巨噬细胞和自然杀伤细胞的活化和侵袭。虽然 许多避免超急性排斥反应的成功策略都已使用 阻止补体级联完全激活的方法， 没有人试图在补体级联反应的最早期抑制补体级联反应， 阶段。补体级联反应初始组分的沉积 (C1、C4、C2）可导致炎性细胞的积聚，并且可 有助于内皮细胞活化，从而产生一种情况， 符合异种移植延迟性排斥反应使用新型合成 肽（互补结合肽）在西北开发 大学，我们将尝试阻止沉积的早期成分 补体级联反应，从而防止超急性排斥反应， 由这些早期刺激引起促炎刺激 件.这将在离体灌注回路中进行测试， 人血通过猪心脏灌注， 互补结合肽。

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.