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悉尼心脏库:在消除或减少人类心脏病动物模型使用的同时,改善转化研究。

The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

作者信息

Dos Remedios C G, Lal S P, Li A, McNamara J, Keogh A, Macdonald P S, Cooke R, Ehler E, Knöll R, Marston S B, Stelzer J, Granzier H, Bezzina C, van Dijk S, De Man F, Stienen G J M, Odeberg J, Pontén F, Linke W A, Linke W, van der Velden J

机构信息

Sydney Heart Bank, Discipline of Anatomy & Histology, University of Sydney, Sydney, Australia.

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, USA.

出版信息

Biophys Rev. 2017 Aug;9(4):431-441. doi: 10.1007/s12551-017-0305-3. Epub 2017 Aug 14.

Abstract

The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170-180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.

摘要

悉尼心脏库(SHB)是现存最大的人体心脏组织库之一。其使命是通过与该领域的专家合作,为研究人类心力衰竭的分子基础提供高质量的人体心脏组织。我们认为,将衰竭的人类心脏组织与年龄匹配的非衰竭健康供体心脏组织进行比较,其结果将比使用动物模型的研究更具相关性,特别是当动物的生理机能与人类差异很大时。心脏手术获取的组织通常必须在采集后尽快使用,否则会显著退化。冷冻是一种选择,但人们担心冷冻会在细胞和分子水平上造成严重损伤。SHB包含心脏移植患者的衰竭样本以及其他为将其组织用于研究而提供知情同意的人的样本。所有样本在从患者身上取出后的40分钟内被保存在液氮中,冠状动脉和左心室样本则在不到5 - 10分钟内完成保存。迄今为止,SHB已从病因广泛的患者身上收集了约450个衰竭心脏的组织(超过15000个样本),以及越来越多肥厚型心肌病患者的心肌切除术样本。该库还拥有来自120多名健康器官供体的心脏,由于各种原因(主要是组织类型与等待心脏移植的受者不匹配),这些心脏无法用于移植。供体心脏由圣文森特医院心肺移植团队从当地医院或距离悉尼4小时喷气式飞行范围内的地方采集。它们用冷心脏停搏液冲洗后运往悉尼,在那里被迅速分成小样本进行冷冻保存。来自世界各地的60多个研究团队使用了衰竭和/或供体样本,并发表了100多篇研究论文。最常被索取的组织来自供体左心室,但右心室、心房、心室间系统和冠状动脉血管的样本也有被报道。所有组织都长期保存在液氮或气相(170 - 180°C)中,并在氮气保护下运输,以避免RNA和巨型蛋白质等敏感分子降解。我们提供的证据表明,这些人体心脏样本的可用性有助于减少人类心力衰竭动物模型的使用。

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