Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; a new source material for bioprosthetic heart valves.
Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; a new source material for bioprosthetic heart valves.
复制标题
野生型和半乳糖α 1,3 半乳糖游离猪心包的物理等效性；生物人工心脏瓣膜的新原料。
DOI：
10.1016/j.actbio.2016.06.007
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发表时间：
2016-09-01
影响因子：
9.7
通讯作者：
Burriesci G
中科院分区：
文献类型：
--
作者：
McGregor C;Byrne G;Rahmani B;Chisari E;Kyriakopoulou K;Burriesci G
人类对具有末端半乳糖α 1，3半乳糖（Gal）修饰的碳水化合物产生高水平的抗体。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衍生的生物医学装置上，包括生物假体心脏瓣膜。人们对使用来自Gal敲除猪（GTKO）的无Gal动物组织越来越感兴趣，因为这些组织不会受到抗Gal抗体介导的损伤的影响。在本研究中，我们比较了标准猪和GTKO猪的戊二醛固定猪心包的组成和生物物理特征。我们表明，除了Gal抗原仅存在于标准猪组织中之外，GTKO和标准猪组织具有相同的一般形态和胶原含量。此外，单轴应力测试和缝线固位测试表明组织的抗拉强度等同。这些研究表明，阻断Gal抗原合成的α-半乳糖基转移酶（GGTA-1）的遗传破坏对猪心包膜的结构完整性没有显著影响，并表明该组织可直接替代生物医学器械（如生物人工心脏瓣膜）中的标准猪心包膜。外科心脏瓣膜置换术是一种经证实的挽救生命的治疗方法，可治疗因出生缺陷、感染和衰老影响而导致的心脏瓣膜功能障碍。由戊二醛固定的动物组织制成的人工生物心脏瓣膜（BHV）是老年患者（>60岁）的有效持久治疗方法，但在年轻患者（<60岁）中表现出年龄依赖性结构性瓣膜退化（SVD）。SVD主要由BHV钙化引起。免疫损伤通过半乳糖α 1，3半乳糖（Gal）（商业BHV上存在的显性异种抗原）和普遍丰富的人抗Gal抗体的相互作用导致年龄依赖性SVD。本研究测量了标准猪心包和来自转基因猪的不含Gal的心包之间的组织等效性，作为制备不含Gal的BHV的第一步。
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 (>60 years) but exhibit age-dependent structural valve degeneration (SVD) in younger patients (<60 years). 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.