Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy

被引：0

作者：

E. V. Dementyeva

S. P. Medvedev

V. R. Kovalenko

Yu. V. Vyatkin

E. I. Kretov

M. M. Slotvitsky

D. N. Shtokalo

E. A. Pokushalov

S. M. Zakian

机构：

[1] Siberian Branch of the Russian Academy of Sciences,Federal Research Center Institute of Cytology and Genetics

[2] Ministry of Health of Russian Federation,Meshalkin National Medical Research Center

[3] Siberian Branch of the Russian Academy of Sciences,Institute of Chemical Biology and Fundamental Medicine

[4] Novosibirsk State University,undefined

[5] Novel Software Systems Ltd,undefined

[6] Moscow Institute of Physics and Technology,undefined

[7] A. P. Ershov Institute of Informatics Systems,undefined

来源：

Biochemistry (Moscow) | 2019年 / 84卷

关键词：

induced pluripotent stem cells; human disease models; hypertrophic cardiomyopathy; cardiomyocytes;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Generation of patient-specific induced pluripotent stem cells (iPSCs) and their subsequent differentiation into cardiomyocytes opened new opportunities for studying pathogenesis of inherited cardiovascular diseases. One of these diseases is hypertrophic cardiomyopathy (HCM) for which no efficient therapy methods have been developed so far. In this study, the approach based on patient-specific iPSCs was applied to create a model of the disease. Genetic analysis of a hypertrophic cardiomyopathy patient revealed R326Q mutation in the MYBPC3 gene. iPSCs of the patient were generated and characterized. The cells were differentiated into cardiomyocytes together with the control iPSCs from a healthy donor. The patient’s iPSC-derived cardiomyocytes exhibited early HCM features, such as abnormal calcium handling and increased intracellular calcium concentration. Therefore, cardiomyocytes obtained by directed differentiation of iPSCs from the HCM patient can be used as a model system to study HCM pathogenesis.

引用

页码：291 / 298

页数：7

共 148 条

[1]

Maron B. J.(2002)Hypertrophic cardiomyopathy: a sys–tematic review JAMA 287 1308-1320

[2]

Maron B. J.(2012)Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives J. Am. Coll. Cardiol. 60 705-715

[3]

Maron M. S.(2014)Hypertrophic cardiomyopathy: a review Clin. Med. Insights Cardiol. 8 53-65

[4]

Semsarian C.(2015)New perspectives on the prevalence of hypertrophic cardiomyopathy J. Am. Coll. Cardiol. 65 1249-1254

[5]

Houston B. A.(1998)A mouse model of myosin bind–ing protein C human familial hypertrophic cardiomyopa–thy J. Clin. Invest. 102 1292-1300

[6]

Stevens G. R.(1999)A transgenic rabbit model for human hypertrophic cardiomyopathy J. Clin. Invest. 104 1683-1692

[7]

Semsarian C.(2002)The L–type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model J. Clin. Invest. 109 1013-1020

[8]

Ingles J.(2007)Mouse models of long QT syndrome J. Physiol. 578 43-53

[9]

Maron M. S.(2016)Induced pluripotent stem cells in the inherited cardiomyo–pathies: from disease mechanisms to novel therapies Trends Cardiovasc. Med. 26 663-672

[10]

Maron B. J.(2006)Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors Cell 126 663-676

← 1 2 3 4 5 6 7 8 9 10 →