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Development of a Gal-free Calcification Resistant Porcine Pericardial Heart Valve.

无加仑抗钙化猪心包心脏瓣膜的开发。

基本信息

批准号：
MR/L013193/1
负责人：
Christopher Mcgregor
金额：
$ 65.15万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FL013193%2F1
关键词：
Development Gal free Calcification Resistant

项目摘要

There are valves in the heart which work to control the normal flow of blood. These valves may be damaged because of birth defects, old age, or after repeated infection with rheumatic fever. If left untreated this is a life threatening condition. There are about 500,000 surgeries to repair or replace heart valves each year. Replacement valves are either mechanical, made of plastic and metal, or biological, made of non-living tissue generally obtained from pigs or cows. Patients and doctors prefer biological heart valves (BHVs) because they work for a long time in older patients, the most frequent group, and do not require daily use of blood thinners which must be used with mechanical valves. In younger adults (30 - 50 years) and in children BHVs wear out rapidly, often within 5 years. These BHVs fail because they build up bone-like deposits of calcium which weaken the valve, leading to tears, or obstruct blood flow because they block the opening of the valve. Scientist and commercial valve companies have long sought to produce BHVs which do not calcify because these could be used in younger patients without the need for blood thinners. So far the calcification blocking treatments which have been developed have been able to greatly reduce valve calcification, when they are tested in animals, but have not been able stop calcification or broaden the use of BHV in younger adults. We have identified an immune driven inflammation which accelerates calcification of biological heart valve materials. This inflammation is unique to humans because a portion of their immune system reacts with a substance, called Gal, not made by people but commonly made in animals and present on the BHV. To block this immune inflammation we have genetically altered pigs so they no longer make Gal and have shown that this Gal-free tissue has a reduced rate of calcification. These Gal knockout pigs are healthy and normal. This project is designed to compare the mechanical function of BHVs made from normal pig tissue with the function of BHVs made from Gal-free tissue. Successfully performing these test which are required by British standards, is the first forward to making a new BHV which resists calcification and may be useful in younger patients

心脏中有控制正常血液流动的瓣膜。这些瓣膜可能因为出生缺陷、年老或反复感染风湿热而受损。如果不治疗，这是一种危及生命的情况。每年大约有50万例手术修复或替换心脏瓣膜。替换瓣膜要么是机械的，由塑料和金属制成，要么是生物的，通常是由猪或牛的非生物组织制成的。患者和医生更喜欢生物心脏瓣膜(BHV)，因为它们在老年患者(最常见的群体)中工作时间很长，而且不需要每天使用血液稀释剂，而血液稀释剂必须与机械瓣膜一起使用。在较年轻的成年人(30-50岁)和儿童中，BHV很快就会磨损，通常在5年内。这些BHV失败是因为它们建立了骨样的钙沉积，削弱了瓣膜，导致撕裂，或者因为它们阻塞了瓣膜的打开而阻碍了血液流动。长期以来，科学家和商业瓣膜公司一直在寻求生产不会钙化的BHV，因为这些产品可以用于更年轻的患者，而不需要血液稀释剂。到目前为止，已经开发的钙化阻断疗法在动物身上进行测试时，已经能够大大减少瓣膜钙化，但还不能阻止钙化或扩大BHV在年轻人中的使用。我们已经确定了一种免疫驱动的炎症，它加速了生物心脏瓣膜材料的钙化。这种炎症是人类独有的，因为他们的免疫系统的一部分与一种名为Gal的物质发生反应，这种物质不是由人类制造的，但通常在动物身上制造，存在于BHV上。为了阻止这种免疫炎症，我们对猪进行了基因改造，使它们不再产生Gal，并表明这种无Gal的组织钙化率降低。这些Gal淘汰猪是健康和正常的。本项目旨在比较正常猪组织和无半乳糖组织制成的BHV的机械性能。成功完成英国标准要求的这些测试，是制造新的抗钙化的BHV的第一步，可能对年轻患者有用

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Initial validation of Gal knockout pig tissues as materials for biological heart valves

Gal基因敲除猪组织作为生物心脏瓣膜材料的初步验证

DOI：
发表时间：
2019
期刊：
XENOTRANSPLANTATION
影响因子：
3.9
作者：
McGregor Christopher
通讯作者：
McGregor Christopher

Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; a new source material for bioprosthetic heart valves.

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
发表时间：
2016-09-01
期刊：
Acta biomaterialia
影响因子：
9.7
作者：
McGregor C;Byrne G;Rahmani B;Chisari E;Kyriakopoulou K;Burriesci G
通讯作者：
Burriesci G

A pig-to-mouse coronary artery transplantation model for investigating the pathogenicity of anti-pig antibody.

DOI：
10.1111/xen.12198
发表时间：
2015-11
期刊：
XENOTRANSPLANTATION
影响因子：
3.9
作者：
Lin, Yi;Miyagi, Naoto;Byrne, Guerard W.;Du, Zeji;Kogelberg, Heide;Gazi, Mozammel H.;Tazelaar, Henry D.;Wang, Chunsheng;McGregor, Christopher G. A.
通讯作者：
McGregor, Christopher G. A.

Does human leukocyte antigens sensitization matter for xenotransplantation?