Today, transplantation of stem / progenitor cells is a promising approach for the treatment of heart diseases. The therapeutic potential of transplanted cells directly depends on the method of delivery to the myocardium, which determines their regenerative properties. It is important for the development of effective methods of cell therapy. In this paper, we performed a comparative study of efficacy of cardiac progenitor cell (CPC) transplantation by intramyocardial needle injections and by tissue engineering constructs (TEC) – “cell sheets” consisting of cells and their extracellular matrix. It has been shown, that transplantation of TEC in comparison with the intramyocardial delivery provides more extensive distribution and retains more proliferating cellular elements in the damaged myocardium, attenuates the negative cardiac remodeling of the left ventricle and promotes its vascularization.

The study of the mechanisms of development and progression of fibrosis is one of the key directions of modern cardiology. Our work suggests that the urokinase receptor (uPAR) is involved in the regulation of mesothelial cell activity and epicardial fibrosis development, which, when interacting with specific ligands and intermediate proteins, can activate intracellular signaling, trigger the cascade of proteolytic reactions, including local plasmin formation and activation of matrix metalloproteinases, providing matrix remodeling.Objective: to perform a comparative study of fibrogenic activity of the epicardium in the hearts of uPAR-/- and wild-type animals and evaluate the effect of cardiac microenvironment factors on the migration activity of epicardial mesothelial cells.Material and methods. We used histological and immunofluorescent staining, microarray analysis of proinflammatory cytokine levels, and a method for assessing the migratory properties of epicardial cells.Results. Results. We found that compared to wild-type animals, uPAR-/- animals show significant thickening of the epicardial area (2.46+0.77 (uPAR-/- mice) and 1.02+0.17 (Wt mice) relative units, P=0.033) accompanied by accumulation of extracellular matrix proteins. Deficiency of uPAR gene leads to formation of proinflammatory microenvironment in the heart (increased levels of proinflammatory factors such as IL-1, IL-13, IL-17, RANTES and MIP1), increased migratory activity of epicardial mesothelial cells, accumulation of TCF21+fibroblast/myofibroblast precursors (29.8+13.7 (uPAR-/- mouse) and 3.03+0.8 (Wt mouse) cells per visual field,P=0.02), as well as development of subepicardial fibrosis.Conclusion. These findings suggest that uPAR is a promising candidate for the developing targeted agents to prevent the development and progression of cardiac fibrosis.

The tentative research was made in 24 rats, Wistar line. The microcirculation level was evaluated in Laser-Doppler flowmetry method and by immunohystochemical visualization of the vessels in the muscles. The chronic ischemia was modeling by cutting out of the femoral artery. The intramuscular introduction of VeGF and intraperitoneal introduction of L-arginine 200 mg/kg were used for treatment. The isotonic solution of NaCl was used in control group. The results were valued in 14-th day. The vessels number increased in groups treated by VeGF and L-arginine. It was statistical difference in microcirculation level between control group and group that was treated by L-arginine.