Is it bad for the heart?
MIPT has grown heart tissue for drug testing
Phys Tech blog, Naked Science
Researchers from the Moscow Institute of Physics and Technology and the Institute of Cytology and Genetics SB RAS have created a test that will determine with high accuracy whether the drug has a side effect in the form of tachyarrhythmia - the most dangerous type of cardiac arrhythmia – or not. The results are published in the journal Toxicological Sciences (Arrhythmogenicity Test Based on a Human Induced Pluripotent Stem Cell (iPSC)-Derived Cardiomyocyte Layer).
Normally, the heartbeat is set by the so-called sinus rhythm. Pacemaker, or "rhythm driver", triggers a wave at the top of the heart. It causes the atrium to contract first, then the ventricles, so the heart pumps blood.
Some chemicals can lead to a parasitic source of excitation that will trigger a wave from another point of the heart. Such sources tend to multiply, which leads to asynchronous contraction of the heart fibers. Fibrillation occurs, which is diagnosed as cardiac arrest.
In fact, everything is trembling and working at the limit, but the blood is not pumping. Therefore, medications are checked for arrhythmogenicity. Initially – on animal cells, then it is the turn of testing on humans. However, the differences between animal cells and human cells are too great, so clinical trials can reveal unexpected side effects.
Scientists have proposed a system that allows testing drugs on human heart cells – cardiomyocytes. At the same time, induced pluripotent stem cells (iPSCs) – cells that can act as stem cells, and they are obtained by genetic manipulation, from ordinary cells of the body, became the building material of the flap of cardiac tissue. It is enough to take a scraping or about 10 milliliters of blood as a basis.
"Cells of any tissue can be obtained from IPSC. But we produce cardiac ones, as they are important for our test. Its minimal applicability is to obtain healthy human cells and use them as a material for testing pharmaceuticals. And the maximum is drawing up a passport of a particular person's sensitivity to various medications, in this case – for the heart. That is, in the future, the technique will become a tool for personalized medicine," said Konstantin Agladze, the first author and head of the Laboratory of Biophysics of excitable systems at MIPT, where the research was conducted.
The resulting heart cells are lined on a substrate in a two-dimensional layer. Since they are able to reproduce on their own, it is not difficult for scientists to produce a sufficient amount for research within a few days. When the test material is ready, an incision is made in it and an excitation wave is triggered using electrical impulses. When she tries to get around an obstacle, a rotating spiral wave appears.
This causes an accelerated heartbeat. Fluorescence and a highly sensitive high-speed video camera help to see and record the whole process. If the addition of the test substance to the cardiac tissue causes a multitude of spiral waves, then this indicates a side effect in the form of cardiac arrhythmia.
Single-arm spiral wave on HL-1 ChR2 cell culture. Frequency: 1.14 Hz. A series of frames displays one period of wave propagation. During one period, the wave front in the form of a spiral makes one revolution around the organizing center / MIPT Press Service
(Figure from the article Galaidych et al. "Optical mapping of excitation waves in photosensitive immortalized cardiomyocyte culture", Proceedings of MIPT, 2013 – WM.)
The results obtained significantly increase the accuracy of the toxicological examination of drugs. In addition, there is no need to conduct such tests on animals. Now scientists are thinking about ways to improve the test. For example, a multi-layered sample will allow for high-performance screening and testing of several dozen chemicals at the same time. However, this technique requires additional research.
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