Mattiuzzo Giada, Scobie Linda, Takeuchi Yasuhiro
Wohl Virion Centre, Division of Infection and Immunity, University College London, London, UK.
Curr Opin Organ Transplant. 2008 Apr;13(2):184-8. doi: 10.1097/MOT.0b013e3282f7961e.
Pig-to-human xenotransplantation has taken steps closer to reality through advances in animal engineering to address immunological as well as microbial problems. The most highlighted problem in xenotransplantation safety has been the potential risk for zoonotic infection mediated by porcine endogenous retroviruses. Safety issues regarding viral zoonosis, particularly porcine endogenous retroviruses, are summarized and commented upon.
Several molecular, transgenic strategies to provide safer transplant source animals with less porcine endogenous retrovirus infectivity have been developed. A genomics approach by selective breeding and porcine endogenous retrovirus loci knockout is at least theoretically possible. For other viruses, advances have been made in technologies for virus discovery and identification.
The consequences of possible zoonoses in xenotransplantation are largely unknown. Further work to identify and control potential zoonotic agents based on recent progress will improve the safety profile of xenotransplantation. Advances made should be subjected to cautious testing in well controlled, preclinical and clinical experiments.
通过动物工程学的进展,猪到人的异种移植在解决免疫以及微生物问题方面已向现实迈进了一步。异种移植安全性方面最突出的问题一直是猪内源性逆转录病毒介导的人畜共患病感染的潜在风险。总结并评论了关于病毒性人畜共患病,特别是猪内源性逆转录病毒的安全问题。
已经开发了几种分子和转基因策略,以提供具有较低猪内源性逆转录病毒感染性的更安全的移植源动物。通过选择性育种和猪内源性逆转录病毒基因座敲除的基因组学方法至少在理论上是可行的。对于其他病毒,在病毒发现和鉴定技术方面也取得了进展。
异种移植中可能的人畜共患病的后果在很大程度上尚不清楚。基于最近的进展,进一步开展工作以识别和控制潜在的人畜共患病原体将改善异种移植的安全性。所取得的进展应在严格控制的临床前和临床试验中进行谨慎测试。