Cardiomyopathy in vitro
Siberian scientists using stem cells to investigate heart disease
Ekaterina Glukhova, "Science in Siberia"
Modern medicine places great hopes on stem cells: the regeneration of diseased organs, the fight against cancer, the restoration and strengthening of the immune system. However, these cells are of interest to scientists not only as a means of therapy, but also as a material for creating models of diseased tissues. At the Institute of Cytology and Genetics SB RAS, a scientific group led by Senior researcher Elena V. Dementieva, Candidate of Biological Sciences, uses stem cells to study hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiovascular diseases (one case per 500 people). In half of the cases, its development is caused by mutations of genes encoding contractile proteins of heart muscle cells (cardiomyocytes). The patient changes the structure of cardiomyocytes, resulting in a thickening of the wall of the left ventricle with a simultaneous decrease in its internal volume and as a result, the contractile function of the heart is disrupted. Patients may develop progressive heart failure, angina pectoris or arrhythmia. The presence and time of symptoms vary greatly: approximately 30% of patients do not feel any problems at all and their first manifestation of GKMP may be sudden death.
Despite the prevalence of the disease and fairly predictable symptoms, scientists still do not understand the mechanisms that underlie its development. To date, medicine can only mitigate the manifestation of dangerous symptoms of HCMP, but not stop its progression.
Cardiomyocytes obtained from a patient with HCMP using IPSC technology. Green color – immunofluorescence staining on the contractile protein of cardiomyocytes, cardiac troponin T. Blue – staining on DNA (cell nucleus). Photo provided by Elena Dementieva.
"The disease has not been sufficiently studied, effective treatment methods have not yet been developed for it, because there are no model systems on which hypertrophic cardiomyopathy could be investigated," says Elena Dementieva. – Patient-specific induced pluripotent stem cells (iPSCs) help to solve this problem. We take blood from patients and isolate mononuclear cells from it, which we then return to an immature state (reprogram), thus obtaining IPSC. They can be differentiated (transformed) into all types of cells of an adult organism, including cardiomyocytes, at any time and in any quantity, which provides unlimited material for research. The cardiomyocytes obtained in this way reproduce all the features of the course of the disease in the donor patient, because they carry the same gene mutations as the cells of his heart."
On the IPSC-cardiomyocytes obtained by directed differentiation, scientists of the Laboratory of Epigenetics of development of the FITF ICiG SB RAS will observe the course of hypertrophic cardiomyopathy caused by various mutations. Once researchers understand what is happening in the "sick" heart cells at the molecular level, it will become easier to develop therapies. Genetic mutations, of course, will not disappear, but it will be possible to more successfully compensate for their effect at the expense of medications and slow down the development of the disease.
The fact that artificial cardiomyocytes are identical to the patient's heart cells is proved by the first result obtained – the detection of disturbances in the dynamics of calcium ion flows. An increased content of calcium ions in cardiomyocytes is one of the early signs of the disease, which manifests itself even before changes at the morphological level become noticeable.
The project "Investigation of the effect of mutations in genes associated with hereditary HCMP on the development of this disease with the help of patient-specific induced pluripotent stem cells" was supported by a grant from the Russian Science Foundation for the event "Conducting research by scientific groups under the leadership of young scientists" of the Presidential Research Projects Program.
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