McGregor Christopher, Byrne Guerard, Rahmani Benyamin, Chisari Elisa, Kyriakopoulou Konstantina, Burriesci Gaetano
University College London, Institute of Cardiovascular Science, United Kingdom.
University College London, Institute of Cardiovascular Science, United Kingdom.
Acta Biomater. 2016 Sep 1;41:204-209. doi: 10.1016/j.actbio.2016.06.007. Epub 2016 Jun 4.
Humans make high levels of antibody to carbohydrates with terminal galactose α 1,3 galactose (Gal) modifications. This Gal antigen is widely expressed in other mammals and is present on an array of current animal derived biomedical devices including bioprosthetic heart valves. There is growing interest in using Gal-free animal tissues from Gal knockout pigs (GTKO) as these tissues would not be affected by anti-Gal antibody mediated injury. In this study we compare the composition and biophysical characteristics of glutaraldehyde fixed porcine pericardium from standard and GTKO pigs. We show that with the exception of the Gal antigen which is only present in standard pig tissue both GTKO and standard pig tissue have the same general morphology and collagen content. Moreover uniaxial stress testing and suture retention testing indicate the tissues are equivalent in tensile strength. These studies indicate that genetic disruption of the α-galactosyltransferase (GGTA-1) which blocks synthesis of the Gal antigen has no significant impact on the structural integrity of porcine pericardium and suggest that this tissue could be directly substituted for standard pig pericardium in biomedical devices such as bioprosthetic heart valves.
Surgical heart valve replacement is a proven life saving therapy to treat heart valve dysfunction due to birth defects, infection and the effects of aging. Bioprosthetic heart valves (BHV) made from glutaraldehyde fixed animal tissues are an effective durable therapy in older patients (>60years) but exhibit age-dependent structural valve degeneration (SVD) in younger patients (<60years). SVD is principally caused by BHV calcification. Immune injury contributes to age-dependent SVD through the interaction of galactose α 1,3 galactose (Gal) a dominant xenogeneic antigen present on commercial BHVs and universally abundant human anti-Gal antibody. This study measures the tissue equivalency between standard pig pericardium and Gal-free pericardium from genetically modified pigs as a first step towards making Gal-free BHVs.
人类会产生针对带有末端半乳糖α1,3半乳糖（Gal）修饰的碳水化合物的高水平抗体。这种Gal抗原在其他哺乳动物中广泛表达，并且存在于一系列当前动物源生物医学装置上，包括生物人工心脏瓣膜。使用来自Gal基因敲除猪（GTKO）的无Gal动物组织的兴趣日益浓厚，因为这些组织不会受到抗Gal抗体介导的损伤影响。在本研究中，我们比较了来自标准猪和GTKO猪的戊二醛固定猪心包的组成和生物物理特性。我们发现，除了仅存在于标准猪组织中的Gal抗原外，GTKO猪组织和标准猪组织具有相同的一般形态和胶原蛋白含量。此外，单轴应力测试和缝线保留测试表明，两种组织的拉伸强度相当。这些研究表明，阻断Gal抗原合成的α-半乳糖基转移酶（GGTA-1）的基因破坏对猪心包的结构完整性没有显著影响，并表明这种组织可以直接替代生物人工心脏瓣膜等生物医学装置中的标准猪心包。
心脏瓣膜置换手术是一种经证实的挽救生命的疗法，用于治疗因出生缺陷、感染和衰老影响导致的心脏瓣膜功能障碍。由戊二醛固定动物组织制成的生物人工心脏瓣膜（BHV）在老年患者（>60岁）中是一种有效的持久疗法，但在年轻患者（<60岁）中会出现年龄依赖性的结构性瓣膜退变（SVD）。SVD主要由BHV钙化引起。免疫损伤通过半乳糖α1,3半乳糖（Gal）——一种存在于商用BHV上的主要异种抗原和普遍存在的人类抗Gal抗体之间的相互作用，导致年龄依赖性SVD。本研究测量了标准猪心包与基因改造猪的无Gal心包之间的组织等效性，作为制造无Gal BHV的第一步。
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