Stem devices: cellular pacemakers will help to recover after a heart attack

For the first time in the world, Russian scientists have studied the process of forming electrical contacts between transplanted heart cells and patient tissues — at the most vulnerable stage, when donor and own cells begin to work as a single system. This was achieved thanks to the creation of an experimental model in which new cells were fixed using polymer microfibers. The results will help develop biological pacemakers in the form of cell patches or injections. Such solutions will compensate for heart failure, correct arrhythmias and accelerate recovery after a heart attack. In addition, the technology opens the way to the creation of a kind of cellular "doping" for the heart, increasing its functionality.

How to replace "broken" heart cells

For the first time in the world, Russian scientists have studied how electrical contacts are formed between transplanted and native heart muscle cells (cardiomyocytes). The data obtained will help create a new generation of pacemakers — bioimplants, that is, pieces of living tissue grown in the laboratory that can replace damaged areas of the heart. The Ministry of Education and Science of the Russian Federation told Izvestia about this.

The study involved specialists from the Moscow Institute of Physics and Technology, the Federal National Medical Research Center for Transplantation and Artificial Organs named after Academician V.I. Shumakov and the National Medical Research Center named after academician E.N. Meshalkin.

— Cardiovascular diseases are one of the main causes of death in the world. In particular, the degeneration of the myocardium (heart muscle) is a serious problem. For example, in the form of scars after a heart attack. The transplantation of cardiomyocytes grown from the patient's own stem cells is considered promising for solving this problem. The technology will make it possible to replace electric pacemakers," Vitaly Dzhabrailov, an engineer at the Laboratory of Experimental and Cellular Medicine at MIPT, told Izvestia.

However, the clinical application of new methods is limited by the fact that the transplanted cells do not always synchronize their work with the surrounding tissue. As a result, uncoordinated contractions can become a source of dangerous arrhythmias. Therefore, it is necessary to know how electrical bridges are established between new and "native" cells after transplantation, he said.

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— To obtain these data, an experimental model was created on rats. First, the scientists grew a layer of cardiomyocytes that mimics the recipient heart. Then the grown cells were transplanted onto it, having previously "seated" them on polymer fibers, which fix the cells on a substrate. Thus, the earliest stage of integration was reproduced in its "pure form", when a new cell is just touching the host tissue," explained Valeria Tsvelaya, head of the Laboratory of Experimental and Cellular Medicine at MIPT.

Transplanted and native cells, she explained, form stable contacts after about a day. The study also examined the initial stage, when cells contract independently of each other, but gradually begin to function as a single tissue. This period is the most vulnerable, because the new cells have not yet fully bonded to the body and the process may go wrong.

The results of the experiment gave an accurate answer to the question of how electrical impulses are carried out by nascent intercellular connections in the first hours. In particular, it turned out that such contacts work about 40 times worse than mature ones, the specialist said. At the same time, the pulse passes with a delay of almost 300 milliseconds, and synchronization of contractions occurs only in 46% of cases.

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— Thus, the work represents a direct measurement of the functional deficit in the first minutes and hours of graft integration. This is fundamentally new information for modeling the risks of arrhythmias in cell therapy. Now we know that there is a window of several hours when the transplanted tissue is electrically vulnerable, and this vulnerability can and should be taken into account," Valeria Tsvelaya emphasized.

According to the researchers, the data obtained can become the basis for the development of safe protocols for cardiac cell therapy. For example, if a patient has heart failure, you can take his stem cells and use them to create a biological pacemaker that will set the right rhythm.

— These can be either special patches with cells (a kind of patches), or injections that contain a suspension of cells on microfibers. Such carriers are needed to stabilize cells and accelerate their contact with surrounding tissues. This technology is not of the near future, but the idea is very promising," said Vitaly Dzhabrailov.

Theoretically, based on this technology, it is possible to imagine means for creating "cellular doping" — increasing the concentration of muscle cells in the heart to increase its capabilities, he added.

Three components for the engraftment of heart cells

— The value of the work lies in the fact that scientists have presented an objective scale of vulnerability of the transplant after contact with the recipient's tissue. This allows us to take a fresh look at the nature of arrhythmogenic risks. Understanding the temporary "risk zone" is important for developing safe cell therapy protocols," Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, corresponding member of the Academy of Sciences of the Republic of Tatarstan, explained to Izvestia.

At the same time, he noted, in the experiment, cells were studied under ideal conditions, but in clinical practice (especially in tissue engineering) bioactive matrices are more often used. They do not just mechanically stabilize the cells, but actively affect them. Such structures accelerate integration, but at the same time introduce additional variables. They are important to consider.

However, in order for cells grown in the laboratory to effectively take root, three components need to be combined, the expert added. First, you need a carrier frame that will deliver and fix them. Secondly, stimulating molecules that will help cells to work properly in a new place. And thirdly, microsensors that will monitor their electrical activity.

"The main problem with such work is that in the next stages it is important to understand how to move from a single—layer model to a three—dimensional one," Philip Kopylov, director of the Institute of Personalized Cardiology at the I.M. Sechenov First Moscow State Medical University, explained to Izvestia.

It turned out that making the right vector of cardiomyocytes in volume so that they all contract in unison and in the right direction is an extremely non—trivial task that has not yet been fully solved. But the next problem is to ensure that the electrical contacts transmit the pulse correctly. And it was her colleagues who approached her decision, the expert noted.