The role of genetically engineered pigs in xenotransplantation research.
The role of genetically engineered pigs in xenotransplantation research.
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DOI：
10.1002/path.4635
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Ayares D
中科院分区：
文献类型：
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作者：
Cooper DK;Ekser B;Ramsoondar J;Phelps C;Ayares D
可用于临床移植的死亡人体器官数量严重短缺。这个问题可以通过移植或基因工程猪的器官来解决，以保护它们免受人类免疫反应的影响。灵长类动物中成功进行猪器官移植的病理生物学障碍包括先天性和适应性免疫系统的激活、凝血失调和炎症。作为器官来源的猪的基因工程已经将移植的猪心脏、肾脏、胰岛和角膜移植物在非人灵长类动物（NHP）中的存活时间从几分钟增加到几个月或偶尔几年。基因工程还可能有助于形成任何可能查明的生理障碍，并减少潜在传染性微生物随器官转移的风险。现在估计有40个或更多的基因改变已经在猪身上进行，有些猪表达5或6个操作。随着新技术的出现，猪表达更多的基因操作将变得越来越普遍，这些基因操作可以在猪-NHP模型中进行测试，以评估其功效和益处。因此，猪肾脏、心脏和胰岛移植的临床试验在不久的将来可能变得可行。
There is a critical shortage in the number of deceased human organs that become available for purposes of clinical transplantation. This problem might be resolved by the transplantation or organs from pigs genetically-engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation, and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in nonhuman primates (NHP) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing 5 or 6 manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart, and islet transplantation will become feasible in the near future.