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一个主要障碍 猪到人的移植，虽然有几种策略， 成功地阻止了这一点。 尽管预防了超急性排斥反应， 发生延迟性异种移植排斥反应，其特征在于内皮细胞 巨噬细胞和自然杀伤细胞的细胞活化和侵袭。 尽管许多成功的避免超急性排斥反应的策略 已经使用了防止补体完全激活的方法 级联，没有人试图抑制补体级联在其 早期阶段 补体起始成分的沉积 级联反应（c1，c4，c2）可导致炎症细胞的积聚 并可能有助于内皮细胞活化， 这种情况与延迟性异种移植排斥反应一致。 使用 开发的新型合成肽（互补结合肽）， 西北大学，我们将试图阻止 补体级联反应的早期成分，从而防止超急性 排斥反应以及促炎刺激， 这些早期的组件。 这将在离体灌注中进行测试 人血通过猪心脏灌注的回路， 没有互补的结合肽。

Because of the severe shortage of available human organs for donations, other species have been considered as potential donors for human transplantation. Of the options available the pig appears to be the most suitable candidates. Hyperacute rejections 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.