2Meshalkin National Medical Research Center, Ministry of Health of Russian Federation, 630055 Novosibirsk, Russia
3Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
4Novosibirsk State University, 630090 Novosibirsk, Russia
5Novel Software Systems Ltd, 630090 Novosibirsk, Russia
6Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Moscow Region, Russia
7A. P. Ershov Institute of Informatics Systems, 630090 Novosibirsk, Russia
* To whom correspondence should be addressed.
Received October 7, 2018; Revised November 25, 2018; Accepted November 25, 2018
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.
KEY WORDS: induced pluripotent stem cells, human disease models, hypertrophic cardiomyopathy, cardiomyocytes