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人类心脏移植项目:心血管医学的转化桥梁。

The Human Explanted Heart Program: A translational bridge for cardiovascular medicine.

机构信息

Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2021 Jan 1;1867(1):165995. doi: 10.1016/j.bbadis.2020.165995. Epub 2020 Oct 22.

Abstract

The progression of cardiovascular research is often impeded by the lack of reliable disease models that fully recapitulate the pathogenesis in humans. These limitations apply to both in vitro models such as cell-based cultures and in vivo animal models which invariably are limited to simulate the complexity of cardiovascular disease in humans. Implementing human heart tissue in cardiovascular research complements our research strategy using preclinical models. We established the Human Explanted Heart Program (HELP) which integrates clinical, tissue and molecular phenotyping thereby providing a comprehensive evaluation into human heart disease. Our collection and storage of biospecimens allow them to retain key pathogenic findings while providing novel insights into human heart failure. The use of human non-failing control explanted hearts provides a valuable comparison group for the diseased explanted hearts. Using HELP we have been able to create a tissue repository which have been used for genetic, molecular, cellular, and histological studies. This review describes the process of collection and use of explanted human heart specimens encompassing a spectrum of pediatric and adult heart diseases, while highlighting the role of these invaluable specimens in translational research. Furthermore, we highlight the efficient procurement and bio-preservation approaches ensuring analytical quality of heart specimens acquired in the context of heart donation and transplantation.

摘要

心血管研究的进展常常受到缺乏可靠的疾病模型的阻碍,这些模型不能完全重现人类的发病机制。这些局限性既适用于基于细胞培养的体外模型,也适用于动物体内模型,这些模型不可避免地受到限制,无法模拟人类心血管疾病的复杂性。在心血管研究中应用人类心脏组织补充了我们使用临床前模型的研究策略。我们建立了人类心脏组织采集计划(HELP),该计划整合了临床、组织和分子表型,从而对人类心脏病进行全面评估。我们的生物标本收集和储存可以保留关键的发病机制发现,同时为人类心力衰竭提供新的见解。使用非衰竭的人类供体心脏作为对照,可以为患病的供体心脏提供有价值的比较组。我们使用 HELP 建立了一个组织库,该组织库已用于遗传、分子、细胞和组织学研究。本综述描述了采集和使用涵盖儿科和成人心脏病谱的人类心脏标本的过程,同时强调了这些宝贵标本在转化研究中的作用。此外,我们还强调了有效的采购和生物保存方法,以确保在心脏捐献和移植背景下获得的心脏标本的分析质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a37d/7581399/072c11ed000e/ga1_lrg.jpg

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