ИСТИНА

Development of cell sheet (CS) technology resulted in a significant advance of cellular-based approaches for induction of regeneration for both – therapeutic use and research needs. The CS is a multilayered complex consisting of viable cells and extracellular matrix proteins that can be manipulated and can be considered as a primitive tissue equivalent. In our study we report on generation of CS from different types of mammalian cells including ones used for cell therapy (mesenchymal stem cells, cardiac primitive cells) and demonstrate their pro-regenerative capacity. We also found evidence of CS to be superior to dispersed cells injections due to higher survival of cells delivered by CS. Furthermore, we established a method to enhance therapeutic potential of CS by expression of VEGF165 by viral transduction and found this to be superior to untreated CS and injected cells in murine model of limb ischemia. A large set of data addresses the “fate” of transplanted cells and we found CS to interact with the host after transplantation, undergo vascularization and certain extent of apoptosis/proliferation in skeletal muscle and myocardium. Overall, we also suggest further directions for the field and present data on hybrid (stem cells + endothelial cells) constructs, CS decellularization and discuss probable application for CS as a technology for study of cellular interactions and tissue formation mechanisms.