Regeneration of the myocardium after ischemia/reperfusion injury


Heart transplantation is currently the only available surgical treatment for a chronic advanced ischemic heart failure. At the same time, despite that the number of patients awaiting transplantation continuously increasing, statistics of usage of this surgery tend to stabilize at certain level in last years. This is due to a lack of donor hearts and presence of serious complications of transplantation, mainly, an occurrence of rejection episodes. It is quite obvious that regenerative technologies that can repair damaged myocardium (cell therapy for ischemic heart disease) can and should be an alternative to transplantation.

These research directions include modification of the stem cell therapy protocol by surrounding mesenchymal stem cells (MSCs) with a semipermeable polymeric membrane allowing gases, liquids, nutrients and signaling molecules to diffuse through. Moreover, encapsulation material protects cells from the recipient's immune system, allowing not only to investigate the predominant mechanism of cardioprotective effects of MSCs, but also to enhance an effectiveness and safety of stem cell therapy. The research project performed together with the Institute of Molecular Biology and Genetics is aimed to answer the one of the most complex and controversial issues of stem cell therapy: a role of paracrine factors in the transplantation of MSCs into ischemic myocardium. Confirmation that the MSCs are potent producers of cardioprotective cytokines may open wide opportunities for the development and rapid implementation of new drugs on the basis of humoral factors and thereby increase the efficiency of stem cell therapy in clinical practice.

Researchers of the Laboratory of Systemic Hemodynamics are testing the hypothesis that programmed cell death is not only an important tool for removing damaged cells from the body, but also is an intensity regulator of organ/tissue cell pool update by stem cells. If this hypothesis is true then it can be assumed that apoptosis products are the feedback factors that may control the proliferation and differentiation of resident cardiomyocyte precursors and may serve as signaling molecules that mediate MSCs migration from blood to myocardium. Understanding of molecular biological characteristics of these signaling structures may offer the challenge to develop an innovative class of drugs, simulators of programmed cell death in organs and tissues.