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Laboratory "Nanostructuring of Membrane-Protein Complexes for the Control of Cell Physiology"

Laboratoty Supervisor: Konstantin Agladze

Since 2010, K. I.Agladze has led the "Nanostructuring of Membrane-Protein Complexes for the Control of Cell Physiology" research laboratory at MIPT under the auspices of the interdisciplinary research and education center "Bionanophysics," of which the main area of research is tissue engineering of the heart. The overall objective of the laboratory is to create artificial tissues that can replace damaged areas of the heart. At this stage, the problem being solved is a three-dimensional framework of polymeric nanofibers, cultivating heart cells to study their effects on various reactions (drugs, bioactive substances, etc.). 

A more distant prospect is the reprogramming of a patient's own cells such as from the skin or heart for growing implants that are compatible with the human body. Tissue engineering of the heart. Recent advances in molecular and cell biology in the last decade have led to rapid development in areas of science such as tissue and cell engineering. In fact, researchers have come close to being able to create body tissues with pre-defined properties. At the core of the project is tissue engineering of the heart. The choice of this path is due to the fact that failures in the cardiovascular system are the leading cause of death in the modern industrialized world.

Tissue engineering of the heart is developed in two main areas. First, the creation of artificial cardiac tissue patches, with a focus on portions of the heart suitable for implantation and damage replacement. It is known that heart tissue is highly structured and has a complex architecture that provides for the robust functionality of this vital organ. The structure of the developed patches is defined by a framework of polymer nanofibers, each of which is capable of carrying cardiac cells and guiding their development. Thus, there appears a kind of "Lego tissue", allowing the creation of highly structured and synchronized contracting cardiac tissue. This approach is a breakthrough because what has been produced so far in the field is an amorphous gel construct of substances with uncertain structural and functional characteristics. 

The second aspect of the study is to investigate the processes that lead to dangerous cardiac arrhythmias, such as rotating-wave excitation, or "reentry", causing disruption of the heart muscle with loss of the ability to maintain blood circulation. Understanding the fundamental mechanisms of the loss of heart tissue stability allows for the development of both conservative-medicated and bloodless surgical (catheter burning ectopic or low-voltage defibrillation) methods for dealing with them. In this way you create fabric constructs intended to serve as experimental models of heart tissue, on which methods of dealing with lethal arrhythmias are studied. They allow you to minimize the complexity and comprehensiveness of the system to the point that the fundamental biophysical mechanisms leading to the disruption of the heart become clear. Recent advances in this area include developing agents allowing the photo-control of cardiac tissue, transferring the substance from the biologically active form into the inactive and vice versa, by irradiating light of different wavelengths. 

There is a third aspect of the project. Currently, the world of science is successfully developing methods for reprogramming cells when differentiated cells are returned to the state of so-called pluripotency similar in their properties to stem cells. These cells are then directed to differentiate into specific tissue cells beforehand. Thus, as an example, a patient's skin cells can be "reprogrammed" to their heart cells. An implantable patch is then created which is fully compatible with the immune system of the donor-recipient. In view of this project, there are plansfor the creation of cultured cardiac tissue from pluripotent cells. Presumably, this trend will become a major research avenue in regenerative medicine in the coming decade.

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