"Valentines" from a test tube
Petri dish with a sick heart
Nadezhda Markina, Infox.ru
To understand the mechanism of heart disease, experts turned skin cells into heart muscle cells, studied the disorders in their work and ... cured the disease.
Cell reprogramming technology has helped the staff of the Stanford University School of Medicine to simulate a model of heart disease and understand its mechanisms at the cellular level. The disease is recognized by a violation of the configuration of the teeth on the electrocardiogram (ECG). The interval between the Q wave and the T wave increases at the same time – the violation is called the long QT interval syndrome. A change in the pattern of electrical activity of the heart indicates a change in the conduction of the heart muscle – the myocardium. Such pathology can lead to dangerous consequences – ventricular arrhythmia and sudden cardiac arrest.
One of the forms of genetically induced prolongation of the QT interval is called Timothy syndrome. Experts know about 10 mutations that cause this disease (they occur in one out of 7 thousand people). But knowing genetic defects is not the same as understanding exactly how they work. To investigate Timothy's syndrome, for example, in mice, is problematic: human and mouse hearts beat too differently: in mice, the frequency of myocardial contractions reaches 500 per minute. And it is difficult to study "in vitro" human heart muscle cells – cardiomyocytes because of the way they are obtained. A heart biopsy is a complex and unsafe procedure.
A heart made of leatherAssociate Professor of neurobiology Ricardo Dolmetsch and his colleagues found a way out in making cardiomyocytes from human skin cells – fibroblasts.
Moreover, the technique of such a transformation is known. The researchers took fibroblasts from the skin of two patients suffering from Timothy syndrome, as well as (for control) from the skin of five healthy volunteers. First, they reprogrammed fibroblasts into pluripotent cells (having the ability to differentiate along multiple pathways, like embryonic stem cells). Then, using biochemical reactions, the scientists turned the resulting cells into cardiomyocytes, which carried the same mutations as the fibroblasts of heart patients. Moreover, different types of cardiomyocytes appeared in the Petri dish – the atrium, ventricle and sinus node (in the latter there are rhythm driver cells that conduct the work of the entire organ). Different types of cells grouped together, creating a miniature model similar to a single-chamber heart.
Find out the cause and choose medications
In this model, the researchers saw differences between the cells of healthy and sick. The "model hearts" were shrinking. Moreover, healthy ones – with a normal heart rate, 60 per minute, and mutant ones – half as often, about 30 per minute (videos can be viewed in the note "Valentine's Day in a dish: heart cells made from skin cells help study, treat disease" on the Stanford University news blog – VM). In addition, the contractions of mutant cardiomyocytes were characterized by irregularity. The action potential – the change in the electrical potential on the cell membrane, which underlies the pulse, turned out to be three times slower in mutant cells than in control cells. Using a confocal microscope and a special indicator for calcium ions, biologists measured calcium conductivity and found that the flow of calcium ions through the membrane was changed in mutant cardiomyocytes.
The result was a cellular model of the long QT interval syndrome, which could be used to search for drugs that would restore normal indicators of electrical activity. Scientists tested one drug on it and made sure that it works. "We have shown that the technology of "diseases in a Petri dish" can be used to test the drug therapy of heart disease," said Ricardo Dolmech.
The scientists wrote about their model in the latest issue of Nature (we could not find the article published on February 9, 2011 in the on-line issue of Nature, but on the Stanford website you can read the press release "Skin cells help to develop possible heart defect treatment in first-of-its-kind study" – VM).
Portal "Eternal youth" http://vechnayamolodost.ru10.02.2011