Today cell therapy is considered as a new perspective approach in the treatment of different structural and functional changes in ischemic myocardium. In the present review we analyze last achievements in autologous stem and progenitor cells use for the regeneration of damaged myocardium at postinfarct heart failure, chronic ischemic cardiomyopathy and chronic heart failure.

Many hopes for increasing the effectiveness of therapy for cardio-vascular diseases such as non optimal for cases of ischemic heart diseases, myocardial infarction, heart failure, critical limb ischemia are connected with progress in gene and cell therapy. Experimental studies strongly demonstrated effective angiogenesis and myocardial regeneration, blood flow restoration in ischemic limb by gene and cell therapy approaches. However the results of clinical studies of these methods are very modest. To overcome the insufficient effectiveness of these methods the genetic modification of stem and progenitor cells - an alliance of gene and cell therapy allowing to neutralize disadvantages and to enhance advantages of both methods - could be used. In this review we have provided an overview of pioneering research in the experimental application of genetically engineered cells in cardiovascular pathology. The possibility of using genetically modified progenitor cells of different origin for therapeutic angiogenesis, myocardial regeneration and creation of cardiac pacemakers is discussed.

The results of hematopoetic stem cell transplantation [HSCTJ of cord blood units collected by Stem Cell Bank of Moscow are described. From August 200Б till August 2009 1Б children with malignant hematological and non-malignant diseases have undergone umbilical cord blood transplantation ШСВТ). The median number of total nucleated cells and CD34+ cells infused was B,Ox107/kg [range 0,2-21,5) and 7,7x105/kg [range 0,5-40), accordingly. 9 (5B,25%) patients showed engraftment. The median time to neutrophil engraftment was 24 days [range 15-ЗБ). Acute GVHD grade l-ll was observed in 7[43,75%) patients, there were no cases of severe GVHD. Chronic GVHD was noted in KB,25%) patient. The transplant-related mortality at 100 days was 28,5%. The overall survival was 5B,2%, with a median time of observation of 11Б days. The results of our study showed that UCB is an alternative source of stem cells for HSCT in patients with malignant and non-malignant diseases.

Earlier we have proposed method for anticalcinosis devitalization of heart valve transplants, which induced total cell death without elimination of cell debris from tissue matrix. It was shown in previous studies prevention of calcinosis in devitalized aorta transplants by the method of subcutaneous implantation in rats. In the present research we investigated biocompatibility of devitalized heart valve alio- and xenografts in the model of chronic implantation in descending aorta of dogs. It was revealed that viable and devitalized aorta grafts became acellular after 4-month implantation. Anticalcinosis divitalization of aorta allografts suppressed immune response, degeneration and calcinosis after their implantation in dogs. Xenografts after anticalcinosis treatment induced strong immune response resulted in fibrous reorganization of tissue matrix. According to the results obtained heart valve allografts devitalized by anticalcinosis treatment can be recommended for clinical trials.

The effects of the allogeneous demineralized bone transplants, seeded with bone marrow-derived multipotent mesenchymal stromal cells CMSCsJ, on the healing of the damaged articular cartilage and the subchondral bone were studied. It was shown that the use of allogeneous as well as autologous MSCs on the demineralized bone transplants and also on the transplants combined with type I collagen gel promote the remodeling of the regenerating tissue and the recovery of the histotypic cartilaginous and osseous structures in comparison with the articular surface regeneration without any therapy or after the procedure of the mosaic chondroplasty. Nevertheless, the positive effects of cell therapy were not clinically prominent, which means most probably in that case that the generally accepted experimental model is not adequate in full measure, but the approach used is promising.

A lot of experimental data have been accumulated and numerous clinical trials have been conducted in the field of stem cell biology in recent years. But still there are many open questions about the survival of transplanted cells, interaction between transplanted cells and recipient microenvironment. That's why it is necessary to develop experimental models of damaged retina which allow studying the behavior of individual cells after transplantation. We used organotypic explantation culture of newborn rat neuroretina as a model to study unfluence of transplanted cells and trophic factors on neuraretina. The advantages of this model are: visualization of transplanted cells, simple analysis of their morphology, survival capacity in neuroretina, interactions with recipient tissue and migration ability. We used newborn rat neuroretina explantation culture (DMEM/F12 with 20ng/mlFGFandEGF, 7% FCS and antibiotics). After 10 days of cultivation retina pigment epithelium cells, MMSC and NSPC from the subventricular brain zone of C57BL/ B-TgCACTB-EGFP)/Osb/J GFP+ mice were transplanted into the cultured neuroretina/ explants. The immunohistochemical staining for [i-lll-tubulin and GFAP was carried out. In our study significant differece in the survival capacity and migration ability of different cell types has been demonstrated, and morphological changes of transplanted cells were have been analyzed.

Transplantation of stem cells, progenitor and differentiated cells is currently actively investigated as an approach for correcting degenerative diseases. However the mechanisms of therapeutic effect of cell therapy remains poorly understood. Nowadays a theory of paracrine stimulation of regeneration processes by transplanted cells through secretion of trophic and growth factors gains a particular popularity. Genetic modification of cells prior to transplantation allows efficient expression and targeted delivery of various therapeutic factors. The use of plasmid expression vectors are considered to be one of the safest and promising approaches for genetic modification of cells. We report generation of genetic constructs based on expression plasmid pBudCE4.1 [containing two independent expression cassettes] encoding different isoforms of human vascular endothelial growth factor (VEGFJ and basic fibroblast growth factor CFGF2). Expression of recombinant proteins was confirmed by immunoblotting and immunochistochemistry. We demonstrated that genetic modification of model cell line HEK293 by our expression plasmids resulted in paracrine stimulation of human umbilical vein endothelial cells CHUVECJ proliferation in vitro.

The effects of autologous mesenchymal stromal cell CMSC) transplantation and of bone marrow IBM) hematopoietic cells mobilization on the course of rhabdomyolysis-induced nephropathy in mice were studied. Both MSC transplantation and mobilization of hematopoietic BM cells were demonstrated to improve function and to inhibit fibrotic transformation of the kidney. At the same time MSC transplantation had no impact on the levels of mononuclear infiltration and on the casts formation, but decreased systemic proinflammatory responsiveness. Mobilization of BM hematopoietic cells, on the contrary, enhanced the levels of mononuclear infiltration and casts formation in renal tissue, but did not alter the systemic proinflammatory responsiveness. Both MSC transplantation and BM hematopoietic cells mobilization were concluded to be the most promising approaches to the development of novel therapeutic methods to treat progressive nephropathy.

The phenomenon of epithelial - mesenchymal plasticity of multipotent mesenchymal stromal cells CMMSCsJ observed in 2D cultures has not been clarified yet. MMSC 3D culturing to model the patterns of epithelial cell layer formation (lamination] gives new opportunities. The review of literature and own findings enabled a suggestion that it is spontaneous formation of MMSC spheroids that induces generation of blastemic tissue in fetal and adult organs when damaged. The feasibility of reprogramming dense MMSC spheroids into neuroectoderm and primitive entoderm has been demonstrated.