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利用人诱导多能干细胞衍生的心肌细胞进行遗传性心脏疾病建模:进展、陷阱和潜力。

Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential.

机构信息

Division Heart and Lungs, Department of Cardiology, Experimental Cardiology Laboratory, Regenerative Medicine Center, University Medical Center Utrecht, Internal Mail No G03.550, GA Utrecht, the Netherlands.

Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

出版信息

Cardiovasc Res. 2018 Dec 1;114(14):1828-1842. doi: 10.1093/cvr/cvy208.

Abstract

In the past few years, the use of specific cell types derived from induced pluripotent stem cells (iPSCs) has developed into a powerful approach to investigate the cellular pathophysiology of numerous diseases. Despite advances in therapy, heart disease continues to be one of the leading causes of death in the developed world. A major difficulty in unravelling the underlying cellular processes of heart disease is the extremely limited availability of viable human cardiac cells reflecting the pathological phenotype of the disease at various stages. Thus, the development of methods for directed differentiation of iPSCs to cardiomyocytes (iPSC-CMs) has provided an intriguing option for the generation of patient-specific cardiac cells. In this review, a comprehensive overview of the currently published iPSC-CM models for hereditary heart disease is compiled and analysed. Besides the major findings of individual studies, detailed methodological information on iPSC generation, iPSC-CM differentiation, characterization, and maturation is included. Both, current advances in the field and challenges yet to overcome emphasize the potential of using patient-derived cell models to mimic genetic cardiac diseases.

摘要

在过去的几年中,利用诱导多能干细胞(iPSCs)衍生的特定细胞类型已发展成为研究多种疾病细胞病理生理学的一种强大方法。尽管在治疗方面取得了进展,但心脏病仍然是发达国家死亡的主要原因之一。揭示心脏病潜在细胞过程的一个主要困难是,能够反映疾病在各个阶段病理表型的存活人类心脏细胞极其有限。因此,定向分化 iPSCs 为心肌细胞(iPSC-CMs)的方法为生成患者特异性心脏细胞提供了一个有趣的选择。在这篇综述中,我们对目前已发表的遗传性心脏病 iPSC-CM 模型进行了全面的综述和分析。除了个别研究的主要发现外,还包括 iPSC 生成、iPSC-CM 分化、特征描述和成熟的详细方法信息。目前该领域的进展和尚未克服的挑战都强调了使用患者来源的细胞模型来模拟遗传性心脏疾病的潜力。

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