Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada.
Am Heart J. 2012 Aug;164(2):177-85. doi: 10.1016/j.ahj.2012.05.011.
There have been significant advances in organ xenotransplantation (cross-species transplantation), especially in the development of genetically engineered pigs, but clinical trials of solid organ transplants are still a time away. However, there is a form of pig-to-human xenotransplantation that has been taking place since the 1960s-bioprosthetic heart valve (BHV) replacement. Recently, there has been increasing evidence that, despite glutaraldehyde fixation of BHVs, there is a significant immune reaction to the valves, leading to calcification, rapid structural deterioration, and failure, particularly in young patients who have a more vigorous immune system and metabolism than the elderly. However, it is the young patients who would most benefit from such BHVs because these avoid the complications associated with the lifelong anticoagulation required with mechanical valves. In this review, we examine pathologic and immunohistochemical reports of failed BHVs that suggest that there is an immune response to these valves. Small animal studies that link the development of calcification and BHV failure to the immune response are reviewed. We draw parallels between the problems of glutaraldehyde-fixed tissue xenotransplantation and those currently being faced in live organ xenotransplantation. Finally, we discuss the advances being made in the production of genetically modified pigs and the evidence that these pigs may become a source of BHVs that can be used worldwide to treat valvular heart disease in children and young adults (for whom there is no ideal valve replacement in existence today). The design of a BHV that is resistant to the host's immune response would be a major step forward in cardiac surgery.
器官异种移植（跨物种移植）取得了重大进展，特别是在基因工程猪的开发方面，但实体器官移植的临床试验仍需时日。然而，自 20 世纪 60 年代以来，已经有一种猪到人的异种移植一直在进行——生物假体心脏瓣膜（BHV）置换。最近，越来越多的证据表明，尽管 BHVs 经过戊二醛固定，但仍会对瓣膜产生明显的免疫反应，导致钙化、结构迅速恶化和失效，尤其是在免疫系统和新陈代谢比老年人更活跃的年轻患者中。然而，正是这些年轻患者最能从这些 BHV 中受益，因为这些 BHV 可以避免与机械瓣膜终生抗凝相关的并发症。在这篇综述中，我们检查了失败的 BHV 的病理和免疫组织化学报告，这些报告表明对这些瓣膜存在免疫反应。我们回顾了将钙化和 BHV 失效与免疫反应联系起来的小动物研究。我们将戊二醛固定组织异种移植存在的问题与目前活体器官异种移植所面临的问题进行了类比。最后，我们讨论了在基因修饰猪生产方面取得的进展，以及这些猪可能成为可在全球范围内用于治疗儿童和年轻成年人瓣膜性心脏病的 BHV 的来源的证据（目前尚无理想的瓣膜置换物可用于这些患者）。设计一种能抵抗宿主免疫反应的 BHV 将是心脏外科的重大进步。
