Modelling sarcomeric cardiomyopathies with human cardiomyocytes derived from induced pluripotent stem cells.
Modelling sarcomeric cardiomyopathies with human cardiomyocytes derived from induced pluripotent stem cells.
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DOI：
10.1113/jp276753
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Campbell SG
中科院分区：
文献类型：
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作者：
Sewanan LR;Campbell SG
源自人类诱导多能干细胞 (iPSC) 的心肌细胞为了解遗传性心肌病突变的病理生理学影响提供了独特的机会。特别是，这些细胞有可能在体外揭示突变对收缩行为的影响，为基因型-表型关系提供新的见解。考虑到这一目标，几个小组已经建立了 iPSC 系，其中含有与患者群体中心肌病相关的肌节基因突变。他们的研究采用了多种系统和方法来执行收缩性的机械测量，从单细胞技术到多细胞组织样结构。在这里，我们回顾了迄今为止在基于 iPSC 的肌节心肌病模型不断发展的领域中发表的结果。我们特别关注在每种情况下选择的机械表征方法，以及这些方法与经典肌肉力学范式的关系。对这些有些微妙的范式的理解可以为比较不同研究的结果并可能协调差异的努力提供信息。尽管仍有更多工作要做，以改进并可能标准化 iPSC 衍生心肌细胞的生产、成熟和机械检测方法，但初步结果表明，这种心肌病建模方法将继续为这些破坏性疾病提供重要见解。在这篇综述中，描述了使用诱导多能干细胞衍生的心肌细胞模拟肌节心肌病领域的当前进展。在许多情况下，开发这些模型的目的是为了表征疾病背后的收缩表型。讨论了用于测量 iPSC 衍生心肌细胞收缩行为的各种方法，并概述了从这些研究中积累的表型数据。
Cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) provide a unique opportunity to understand the pathophysiological effects of genetic cardiomyopathy mutations. In particular, these cells hold the potential to unmask the effects of mutations on contractile behaviour in vitro, providing new insights into genotype–phenotype relationships. With this goal in mind, several groups have established iPSC lines that contain sarcomeric gene mutations linked to cardiomyopathy in patient populations. Their studies have employed diverse systems and methods for performing mechanical measurements of contractility, ranging from single cell techniques to multicellular tissue-like constructs. Here, we review published results to date within the growing field of iPSC-based sarcomeric cardiomyopathy disease models. We devote special attention to the methods of mechanical characterization selected in each case, and how these relate to the paradigms of classical muscle mechanics. An appreciation of these somewhat subtle paradigms can inform efforts to compare the results of different studies and possibly reconcile discrepancies. Although more work remains to be done to improve and possibly standardize methods for producing, maturing, and mechanically interrogating iPSC-derived cardiomyocytes, the initial results indicate that this approach to modelling cardiomyopathies will continue to provide critical insights into these devastating diseases. In this review, current progress in the field of modelling sarcomeric cardiomyopathies using induced pluripotent stem cell-derived cardiomyocytes is described. In many cases, these models have been developed for the purpose of characterizing the contractile phenotype that underlies disease. The various methods that have been employed to measure contractile behaviour of iPSC-derived cardiomyocytes are discussed and an overview of the phenotypic data that are accumulating from these studies is provided.