Modeling hypertrophic cardiomyopathy with human cardiomyocytes derived from induced pluripotent stem cells.
Modeling hypertrophic cardiomyopathy with human cardiomyocytes derived from induced pluripotent stem cells.
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DOI：
10.1186/s13287-022-02905-0
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发表时间：
2022-06-03
影响因子：
7.5
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中科院分区：
文献类型：
--
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研究肥厚型心肌病（HCM）发病机制的障碍之一是在疾病发展的早期阶段心肌组织样品的可获得性差。诱导多能干细胞（iPSC）的出现解决了这一问题，它使我们能够在体外将患者来源的iPSC分化为心肌细胞（iPSC-CM）。本文综述了iPSC模型的建立方法以及基因组编辑技术在iPSC中的应用。由于现阶段培养的iPSC-CM在结构和功能上都不成熟，研究人员尝试了几种方法来成熟iPSC-CM，例如延长培养时间，机械和电刺激。目前，许多研究人员已经建立了HCM的iPSC-CM模型，并采用多种方法进行细胞形态，收缩性，电生理特性，钙处理，线粒体功能和代谢的测量。在这里，我们回顾了迄今为止在HCM的iPSC-CM模型的日益增长的领域内在人类中发表的结果。虽然没有统一的共识，但初步结果表明，这种疾病建模方法将为我们理解HCM发病机制提供重要见解，并促进药物开发和安全性测试。
One of the obstacles in studying the pathogenesis of hypertrophic cardiomyopathy (HCM) is the poor availability of myocardial tissue samples at the early stages of disease development. This has been addressed by the advent of induced pluripotent stem cells (iPSCs), which allow us to differentiate patient-derived iPSCs into cardiomyocytes (iPSC-CMs) in vitro. In this review, we summarize different approaches to establishing iPSC models and the application of genome editing techniques in iPSC. Because iPSC-CMs cultured at the present stage are immature in structure and function, researchers have attempted several methods to mature iPSC-CMs, such as prolonged culture duration, and mechanical and electrical stimulation. Currently, many researchers have established iPSC-CM models of HCM and employed diverse methods for performing measurements of cellular morphology, contractility, electrophysiological property, calcium handling, mitochondrial function, and metabolism. Here, we review published results in humans to date within the growing field of iPSC-CM models of HCM. Although there is no unified consensus, preliminary results suggest that this approach to modeling disease would provide important insights into our understanding of HCM pathogenesis and facilitate drug development and safety testing.
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