Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep.
Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep.
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DOI：
10.1007/s13239-021-00585-0
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发表时间：
2022-06
影响因子：
1.8
通讯作者：
Byrne, Guerard
中科院分区：
文献类型：
--
作者：
McGregor, Christopher;Salmonsmith, Jacob;Burriesci, Gaetano;Byrne, Guerard
应用基因工程降低抗原性的动物组织制造人工生物心脏瓣膜（BHV）以减少抗体诱导的组织钙化和加速的结构性瓣膜退化（SVD）的兴趣越来越大。本研究在绵羊二尖瓣植入90天后，测试了由GalKO（GalKO）和标准猪心包膜制成的瓣膜的生物等效性。GalKO（n = 5）和标准（n = 5）猪心包BHV以随机和盲法植入绵羊体内90天。每隔30天测量一次瓣膜血流动力学功能。瓣膜置换后，检查瓣膜是否有血管翳、赘生物、炎症、血栓和组织钙化。10名受试者中有9人完成了研究。两个研究组之间的血流动力学性能没有差异，没有瓣膜相关不良事件。取出的BHV显示出轻度血管翳整合和极轻微的血栓，两组之间没有差异。X射线探测到有限的焦点矿床。原子光谱分析检测到GalKO BHV的组织钙水平为1.0 µg/mg ± 0.2，标准组织BHV为1.9 µg/mg ± 0.9（p = 0.4），认为两者均较低且等同。这是首次证明GalKO与标准猪心包之间的生物等效性。GalKO突变既不会对BHV性能造成内在的有害生物学影响，也不会对BHV性能产生功能影响。GalKO组织用于手术或经导管BHV的商业适应性将消除产生抗Gal抗体的患者与含有Gal抗原的BHV之间的临床差异。GalKO BHV可以减少加速的组织钙化和SVD，增加患者的选择，特别是对于年轻患者。在线版本包含补充材料，可通过10.1007/s13239-021-00585-0获得。
There is growing interest in the application of genetically engineered reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves (BHVs) to reduce antibody induced tissue calcification and accelerated structural valve degeneration (SVD). This study tested biological equivalence of valves made from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral valve implantation in sheep. GalKO (n = 5) and standard (n = 5) porcine pericardial BHVs were implanted in a randomized and blind fashion into sheep for 90-days. Valve haemodynamic function was measured at 30-day intervals. After explantation, valves were examined for pannus, vegetation, inflammation, thrombus, and tissue calcification. Nine of 10 recipients completed the study. There was no difference between study groups for haemodynamic performance and no adverse valve-related events. Explanted BHVs showed mild pannus integration and minimal thrombus, with no difference between the groups. Limited focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis detected tissue calcium levels of 1.0 µg/mg ± 0.2 for GalKO BHVs and 1.9 µg/mg ± 0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. This is the first demonstration of biological equivalence between GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic detrimental biological nor functional impact on BHV performance. Commercial adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the clinical disparity between patients producing anti-Gal antibody and BHVs containing the Gal antigen. GalKO BHVs may reduce accelerated tissue calcification and SVD, enhancing patient choices, especially for younger patients. The online version contains supplementary material available at 10.1007/s13239-021-00585-0.
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影响因子：
1.5
作者：
Mangold, A.;Szerafin, T.;Ankersmit, H. J.
通讯作者：
Ankersmit, H. J.
影响因子：
4.6
作者：
Flameng, Willem;Meuris, Bart;Herregods, Marie-Christine
通讯作者：
Herregods, Marie-Christine
影响因子：
1.6
作者：
Neethling, WML;Hodge, AJ;Glancy, R
通讯作者：
Glancy, R
DOI：
10.1016/j.jtcvs.2014.09.062
发表时间：
2015-01-01
影响因子：
6
作者：
Flameng, Willem;Hermans, Hadewich;Meuris, Bart
通讯作者：
Meuris, Bart
DOI：
10.1016/j.jtcvs.2010.08.064
发表时间：
2011-01-01
影响因子：
6
作者：
McGregor, Christopher G. A.;Carpentier, Alain;Byrne, Guerard W.
通讯作者：
Byrne, Guerard W.