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心肌切片:转化心血管研究的中间复杂性平台。

Myocardial Slices: an Intermediate Complexity Platform for Translational Cardiovascular Research.

机构信息

National Heart & Lung Institute, Imperial College London, London, UK.

出版信息

Cardiovasc Drugs Ther. 2019 Apr;33(2):239-244. doi: 10.1007/s10557-019-06853-5.

Abstract

Myocardial slices, also known as "cardiac tissue slices" or "organotypic heart slices," are ultrathin (100-400 μm) slices of living adult ventricular myocardium prepared using a high-precision vibratome. They are a model of intermediate complexity as they retain the native multicellularity, architecture, and physiology of the heart, while their thinness ensures adequate oxygen and metabolic substrate diffusion in vitro. Myocardial slices can be produced from a variety of animal models and human biopsies, thus providing a representative human in vitro platform for translational cardiovascular research. In this review, we compare myocardial slices to other in vitro models and highlight some of the unique advantages provided by this platform. Additionally, we discuss the work performed in our laboratory to optimize myocardial slice preparation methodology, which resulted in highly viable myocardial slices from both large and small mammalian hearts with only 2-3% cardiomyocyte damage and preserved structure and function. Applications of myocardial slices span both basic and translational cardiovascular science. Our laboratory has utilized myocardial slices for the investigation of cardiac multicellularity, visualizing 3D collagen distribution and micro/macrovascular networks using tissue clearing protocols and investigating the effects of novel conductive biomaterials on cardiac physiology. Myocardial slices have been widely used for pharmacological testing. Finally, the current challenges and future directions for the technology are discussed.

摘要

心肌切片,也称为“心脏组织切片”或“器官型心脏切片”,是使用高精度振动切片机制备的活的成年心室心肌的超薄切片(100-400μm)。它们是一种中等复杂度的模型,因为它们保留了心脏的固有细胞多样性、结构和生理学,而其薄片确保了体外有足够的氧气和代谢底物扩散。心肌切片可以从多种动物模型和人类活检中制备,从而为转化心血管研究提供了一个有代表性的人类体外平台。在这篇综述中,我们将心肌切片与其他体外模型进行了比较,并强调了该平台提供的一些独特优势。此外,我们还讨论了我们实验室为优化心肌切片制备方法所做的工作,该方法仅使 2-3%的心肌细胞受损,就能从大型和小型哺乳动物心脏中制备出高度存活的心肌切片,并且保留了结构和功能。心肌切片的应用涵盖了基础和转化心血管科学两个方面。我们实验室利用心肌切片研究了心脏的细胞多样性,使用组织透明化方案可视化 3D 胶原分布和微血管/大血管网络,并研究了新型导电生物材料对心脏生理学的影响。心肌切片已广泛用于药理学测试。最后,讨论了该技术当前的挑战和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34c/6509068/af886a85c5c4/10557_2019_6853_Fig1_HTML.jpg

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