Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Division of Pediatric Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Ann Thorac Surg. 2019 Aug;108(2):624-635. doi: 10.1016/j.athoracsur.2019.01.054. Epub 2019 Mar 2.
Bioprosthetic heart valves undergo structural degeneration and calcification. Similarities exist in the histopathologic features of explanted bioprosthetic valves and rejected pig tissues and organs after xenotransplantation into nonhuman primates. The development of more durable bioprosthetic valves, namely from genetically modified pigs, could negate the need for the insertion of mechanical prostheses in children and young adults with the requirement for life-long anticoagulation and might avoid the need for reoperation in elderly patients.
We reviewed the literature (MedlinePlus, PubMed, Google Scholar) through September 1, 2018, under four key terms: (1) bioprosthetic heart valves, (2) xenograft antigens, (3) immunologic responses to bioprosthetic valves, and (4) genetic modification of xenografts.
Advances in tissue and organ xenotransplantation have elucidated important immunologic barriers that provide innovative approaches to prevent structural degeneration of bioprosthetic heart valves. The current evidence suggests that bioprosthetic valves derived from genetically modified pigs lacking xenogeneic antigens (namely Gal, Neu5Gc, and Sda), termed triple-knockout pigs, would function considerably longer than current wild-type (genetically unmodified) porcine valves in human recipients.
Preclinical and clinical studies to determine the safety and efficacy of triple-knockout porcine bioprosthetic valves will likely establish that they are more resistant to human immune responses and thus less susceptible to structural degeneration.
生物瓣心脏瓣膜会发生结构退化和钙化。在被异种移植到非人类灵长类动物后的已植入的生物瓣和被排斥的猪组织和器官的组织病理学特征中存在相似性。开发更耐用的生物瓣，即来自基因修饰猪的生物瓣，可以避免儿童和年轻人对终身抗凝的需求，并避免老年患者需要再次手术。
我们通过四个关键术语回顾了文献（MedlinePlus、PubMed、Google Scholar），这些术语是：（1）生物瓣心脏瓣膜，（2）异种移植物抗原，（3）对生物瓣的免疫反应，和（4）异种移植物的基因修饰。
组织和器官异种移植的进展阐明了重要的免疫障碍，为防止生物瓣心脏瓣膜结构退化提供了创新方法。目前的证据表明，缺乏异种抗原（即 Gal、Neu5Gc 和 Sda）的基因修饰猪来源的生物瓣（称为三重敲除猪）在人类受者中比目前的野生型（基因未修饰）猪生物瓣功能更持久。
确定三重敲除猪生物瓣的安全性和有效性的临床前和临床研究可能表明，它们对人体免疫反应的抵抗力更强，因此结构退化的可能性更小。
