RESUMEN
Hypertrophic cardiomyopathy (HCM) is a frequent cardiovascular pathology caused by a huge number of mutations in sarcomere-associated proteins. This genetic diversity leads to differences in pathogenetic mechanisms and hampers HCM therapy. Cardiomyocytes derived from patient-specific induced pluripotent stem cells give new opportunities for studying underlying HCM mechanisms. We generated an iPSC line from peripheral blood mononuclear cells of an HCM patient with a heterozygous p.E510Q mutation in HADHA using non-integrating episomal vectors. The iPSC line showed typical morphology, expression of pluripotency markers, capacity to be differentiated into derivatives of three germ layers, and presence of the patient-specific mutation.
Asunto(s)
Cardiomiopatía Hipertrófica , Células Madre Pluripotentes Inducidas , Cardiomiopatía Hipertrófica/genética , Heterocigoto , Humanos , Leucocitos Mononucleares , Subunidad alfa de la Proteína Trifuncional Mitocondrial , MutaciónRESUMEN
Hypertrophic cardiomyopathy (HCM) is one of the most frequent cardiovascular diseases but no methods to prevent its progression have been developed. Cardiomyocytes derived from patient-specific induced pluripotent stem cells can become a platform to study pathogenesis of the disease and to search for more effective therapy methods. We generated two iPSC lines from peripheral blood mononuclear cells of an HCM patient with heterozygous p.M659I mutation in MYH7 using episomal vectors. The iPSC lines expressed pluripotency markers, demonstrated ability to spontaneously differentiate into derivatives of three germ layers, and retained the mutation.
Asunto(s)
Cardiomiopatía Hipertrófica , Células Madre Pluripotentes Inducidas , Miosinas Cardíacas/genética , Cardiomiopatía Hipertrófica/genética , Diferenciación Celular , Humanos , Leucocitos Mononucleares , Mutación , Cadenas Pesadas de Miosina/genéticaRESUMEN
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.