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

被引：13
|
作者：
Dementyeva, E. V. [1 ,2 ,3 ]
Medvedev, S. P. [1 ,2 ,3 ,4 ]
Kovalenko, V. R. [1 ,2 ,3 ,4 ]
Vyatkin, Yu. V. [4 ,5 ]
Kretov, E. I. [2 ]
Slotvitsky, M. M. [6 ]
Shtokalo, D. N. [5 ,7 ]
Pokushalov, E. A. [2 ]
Zakian, S. M. [1 ,2 ,3 ,4 ]
机构：
[1] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Fed Res Ctr, Novosibirsk 630090, Russia
[2] Minist Hlth Russian Federat, Meshalkin Natl Med Res Ctr, Novosibirsk 630055, Russia
[3] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk 630090, Russia
[4] Novosibirsk State Univ, Novosibirsk 630090, Russia
[5] Novel Software Syst Ltd, Novosibirsk 630090, Russia
[6] Moscow Inst Phys & Technol, Dolgoprudnyi 141701, Moscow Region, Russia
[7] AP Ershov Inst Informat Syst, Novosibirsk 630090, Russia
来源：
BIOCHEMISTRY-MOSCOW | 2019年 / 84卷 / 03期
基金：
俄罗斯科学基金会;
关键词：
induced pluripotent stem cells; human disease models; hypertrophic cardiomyopathy; cardiomyocytes; GENETICS;
D O I：
10.1134/S0006297919030118
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
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
收藏
页码：291 / 298
页数：8
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