ИСТИНА

Recently cell-based therapies have emerged as an alternative for cardiac transplantation and a method for repair of damaged heart. Among the tested cell types progenitor cells isolated from postnatal heart are one of the most potentially applicable for cell-based therapy due to their considerable regenerative potential for impaired heart tissue shown in experimental and clinical settings. However, poor retention and viability of transplanted cells delivered by direct injection of cell suspension into impaired myocardium or into coronary circulation are the main obstacles in this field restricting therapeutic benefits of cell therapy. To overcome these challenges cell sheet (CS) technology has been developed as a means of permitting longer retention and better viability of graft cells. We assembled c-kit+ Lin-cardiac progenitor cells and cardiosphere-derived cells into scaffold-free CSs using temperature-responsive cell culture dishes. Both type of CSs were shown to secrete growth factors and extracellular matrix (ECM) proteins providing an appropriate cellular micro-environment. Implantation of these constructs on epicardial surface in a rat model of acute myocardial infarction provided better cell survival and engraftment than control delivery of the same amount of cells by injection. Intensive migration of CSC from the sheets to area of infarction was observed. Transplanted cells proliferated within CSs and expressed markers of endothelial and cardiogenic differentiation. Significant vascularization of CSs and underlying border and infarct zones were observed. CSs implantation reduced post-infarction structural myocardial remodelling and fibrosis. It is intriguing to note that CS implantation stimulated cardiomyocytes proliferation in both –border and infarction zones. Our results suggest that delivery of cardiac progenitor cells as cell sheets to infarcted heart could be a promising approach to stimulate myocardial angiogenesis and induce regeneration. Possible mechanisms of angiogenic and regenerative effects of cardiac will be discussed