The 6 types of cross-linked autobodies of one family where identified during relapsing course of Ulcerativ Colities (UC) acompanied with deterioration of clinical and endoscopic activity and increasing rate of acut inflammatory phase (CRP, number of leukocytes and erythrocyte sedimentation rate) of the disease. On the background of transplantation of mesenchymal bone marrow stromal cells (BM MSC), and despit the identification of six types of autoantibodies to antigens of neutrophils, was observed moderate activity of UC and low concentration of autoantibodies than in immunosuppressive therapy without BM MSC transplantation. Discovered anti-inflammatory effect of BM MSCs transplantation in UC may be explained by the systemic influence of immunosuppressive effect: it is known that the BM MSCs inhibit dendritic cells, T-and B-lymphocytes participating in the immune response, activate regulatory T-cells, which produce antinflammatory cytokines, IL-10 and TGF-1beta, which suppress the inflammatory process.

Clinical observations and studies have shown that among 34 patients with Crohn's disease (CD) under infliximab (INFX) therapy in 8.8% cases was observed the loss of response to anticytokine therapy (so-called primary ineffectiveness of anti-cytokine therapy (ACT)). The increasing of INFX dosage up to 10 mg/kg of body weight failed to achieve clinical and endoscopic remission. It should be noted that, despite the long anticytokine therapy in these patients the antibodies to INFX were not observed and INFX concentration in blood serum practically was not determined. In CD patients with primary ineffectiveness of anti-cytokine therapy (ACT) was detected clinical deterioration of CD: increase of WR Best Index (CDAI), appearance of pain, fever, increase of stool frequency with blood and mucus, improving performance of acute phase of inflammation. Transplantation of mesenchymal bone marrow stromal cells (MSC) enhanced the level of INFX in the serum and overcoming the primary ineffectiveness of anti-cytokine therapy (ACT) and increase in sensitivity to Infliximab.

During the last decade, stem cell research has developed at an accelerated pace. Various types of stem cells have been tested for myocardial infarction therapy. Despite the preclinical benefits of cell therapy success in clinical trials remains modest. The main obstacles to regeneration of the infarcted heart using stem cells are: 1) not every stem cell type can differentiate into cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been shown to improve transplantation efficacy of mesenchymal stem cells and cardiac progenitor cells in animal models of myocardial infarction. It has also been shown that transplantation of preconditioned cells decreases infarct size, prevents postinfarction remodeling of the heart, and positively modulates development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents extensive death of transplanted cells due to necrosis and apoptosis during long-term hypoxia or oxidative stress. The protective effect of HP is based on three main processes: (1) modification of cell phenotypes to help survival during hypoxia (enhancement of HIF-1alpha expression, ERK1/2 and Akt activation, enhancement of erythropoietin receptor expression and erythropoietin production, and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2) upregulation of various secretable factors including the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2 and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors, which play an important role in mobilization and homing of stem cells in the ischemic region.

Literature review contains the literature data and the results of author's own investigations describing the coming into being and the development of the concepts on the regeneration of endocrine gastroenteropancreatic (GEP) system under the conditions of norm, experimental and clinical pathology. Data analysis permitted to reveal the similarities and differences in the course of this process in various organs of the digestive system. Endocrine GEP system renewal occurs at different levels of its organization. At the tissue level, the endocrine cells renewal occurs via the transformation of exocrine cells into the endocrine ones and as a result of differentiation from stem cells via the "agranular" cell stage which are precursors of the endocrine cells. This pathway of regeneration is the major one after the damage. Regeneration at cellular level occurs through mitotic division of the differentiated endocrine cells (early stage of regeneration) and as a result of the formation granules with different hormonal profile in D-cells. At the intracellular level, the regeneration is realized through the intracellular structure restoration after their damage induced by the increase of cell functional activity accompanied by degranulation and dystrophic changes development

The distribution of nitroxide ergic neurons in the medulla oblongata nuclei in Wistar rats (n = 8) was studied histochemically (NADPH-diaphorase) and using immunohistochemistry with an antiserum against neuronal form of nitric oxide synthase (nNOS). NADPH-diaphorase activity was found in large and small neurons of the sensory, autonomic and motor nuclei. The latter were especially rich in the cells demonstrating the activity of the enzyme. Unlike NADPH-diaphorase, nNOS in the corresponding nuclei was always detected in the fewer number of neurons, predominantly of small sizes. The sensory nuclei (nucleus of solitary tract, reticular parvocellular and lateral nuclei, spinal nucleus of the trigeminal nerve) contained 1.5-3 times more nNOS neurons than in motor nuclei. In some nuclei (nucleus ambiguus, hypoglossal nerve nucleus), containing numerous NADPH-diaphorase-positive neurons, immunoreactive cells were particularly rare.

Folliculo-stellate cells are known as S-100 protein immunopositive cells of the anterior lobe of pituitary gland which are not secreting hormones and are presumed to be organ specific stem cells of the adenohypophys. Their role in adaptation of the body to stress remains unclear.

AIM. To study the elements of the mesenchymal stromal cell compartment (multipotent mesenchymal stromal cells (MMSCs)) and their more mature progenies of fibroblast colony-forming units (CFU-F) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS. The total production of MMSCs after 5 passages, the time of their growth, and the concentration of CFU-F in the bone marrow from patients were determined using the control sections before transplantation and over time for 2 years after allo-HSCT. What is more, the genetic affiliation of the MMSCs from the patients after allo-HSCT and their immunophenotype were studied.

To study biological (cell and anticytokine) therapy-induced changes in the levels of proinflammatory cytokines in patients with inflammatory bowel diseases (IBD).

Review is devoted to a comparative analysis of stem cells migration methods for studying in experimental conditions and clinics, assessing their strengths and weaknesses. It is impossible to single out any one preferred method for studying the migration of stem cells. Each method has its own set of advantages and disadvantages. X-ray methods "suffer" from non-specific binding of contrast marks, followed by rapid degradation and the release of the body. If it is necessary to study the migration of the transplanted stem cells for a long time interval, the visualization of the reporter gene is the best available techniques, since it can provide a non-invasive real time monitoring of the location in the tissue and stem cells isolated help assess their viability and proliferation. The most attractive of the agents for monitoring--endogenous, i.e. natural constituents stem cells, for example, genetic markers. Criteria for the application of methods to study migration in clinical and experimental results have significant differences. The main criteria for the methods of the study of cell migration in clinical settings, it must be biocompatible, safe, non-toxic, non-invasive. Accordingly, the main criteria for the experimental methods for studying the migration will be accuracy, the ability to quantify the long-term migration of cells and stability of the "label".

In present publication we describe for the first time the obtainment of cancer stem cells from a weakly metastatic human colorectal carcinoma cell line MIP101 via selecting from the native population the cells that express intensively an embryonic stem cell marker, POU5F1 (Oct4). We provide the evidence that these cells possess an elevated clonogenic and tumorigenic potential when compared to the native population, and this correlates to the hypothesis of cancer stem cells' primary role in the development of malignant neoplasms.

Mutations in lamin A/C gene (LMNA) lead to development of severe disorders--laminopathies. Unlike most other types of intermediate filaments, where the pathological effect of mutations is tightly linked to alteration of mechanical and integrative functions, the detailed mechanism of lamin mutations is still unclear and possibly involves the alteration of nuclear signaling and transcriptional processes. Since the mesenchymal lineage tissues such as myocardium, skeletal muscle, adipose and bone tissues are mostly affected in laminopathies, the role of lamin A/C in differentiation process of mesenchymal stem cells has been assumed. The aim of the study was to estimate the effect of LMNA mutations of differentiation of mesenchymal stem cells into adipose lineages. In vitro mitagenesis was performed on wild type LMNA gene incorporated in a lentiviral vector. Several previously described mutations in LMNA were used, each associated with a certain phenotype. Adipose-derived mesenchymal stem cells from healthy donors were transduced with lentiviruses bearing either wild-type or mutant LMNA. Cells were then induced to adipose differentiation. We show that mutant LMNA/C promotes differentiation capacity of mesenchymal stem cells as seen by morphological changes and by expression of specific adipose markers.

Elaboration of the concept of neural stem cells at the end of the twentieth century resulted in the appearance of the multitude of new terms used for the designation of cells localized in the proliferative zones of the brain. Concurrently, a problem arose concerning the correlation of newly named cells, generally known elements of the nervous tissue, and classic views on its development. In the present study, an attempt is made on the basis of the literature data review and authors' own experience in the exploration of proliferative zones, to classify cell populations involved in the neurogenesis considering, primarily, the possibilities of their morphological and immunocytochemical in situ identification.

The perspectives of use of porous polytetrafluorethilen (PTPE) with modified surface combined with mesenchymal stem cells for tissue-engineering constructions were studied. The paper also describes the mode of PTPE surface modification consisting in nanostructured metallic or ceramic layer application resulting in biocompatibility and surface adhesion rates increase. The magnetic atomizing of Ti and Ti-Ca-P-C-O-N nanolayers enhances the material integration potential as well as adhesion rates thus making it perspective when combined with mesenchymal stem cells for bone defects plasty.

Using the methods of luminescent microscopy, the results of injection of autologous multipotent stromal (mesenchymal) stem cells of bone marrow origin (SSCBMO) containing GFP gene, into thrombosed hindlimb vein were studied in 226 male Wag rats. It was found that the restoration of blood flow through the thrombosed main vein was not always the result of thrombolysis. No signs of incorporation of injected SSCBMO into the wall of thrombosed vessel, clot recanalization or collateral formation were detected. In experimental thrombosis model with thrombin administration and main vein ligation, the thrombosis of its small branches also took place. The restoration of blood flow occured via either blood clot recanalization or obliteration of thrombosed vessels and the outgrowth of the new ones. SSCBMO were found to participate in both of these processes resulting in faster restoration of a blood flow in the tissue microregion of thrombosed vein. Gradually the injected SSCBMO and the structures formed with their participation, were replaced by the own cells of a recipient organism.

Effects of immediate single transplantation of human umbilical cord blood mononuclear cells (UCB-MC) transfected with recombinant vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF2) genes into the area of injury were studied on the model of rat spinal cord dosed contusion at TVIII level. UCB-MC transfected with EGFP-N2 plasmid were transplanted into the rats of the control group under similar conditions. The presence of EGFP- labeled cells were traced in white matter during 21 days after transplantation at a distance no less than 10 mm in rostral and caudal directions from the nearest point of the injection. By 30 days after the transplantation of UCB-MC transfected with pBud-VEGF-FGF2 plasmid, the cross-sectional area of sparing grey matter increased by more than 60% at a distance of 3 mm from the epicenter of injury. By that time, in the animals of this group, the number of perivascular cells expressing beta receptor of platelet-derived growth factor (PDGFbetaR) was increased by an average of 30% in the outer zones of white matter 1.5 cm from the injury epicenter. Delivery of the therapeutic genes VEGF and FGF2 to the damaged region and their expression in cell carriers stimulates vascularization and post-traumatic spinal cord regeneration.

Nestin and Musashil (Msi-1) proteins are most often used for labeling of neural stem cells and progenitor cells in vivo, however it remains unclear if these markers really label the same cells. As a result of the study of structural characteristics and localization of nestin- and Msil-expressing cells it was found that these proteins were detected in non-identical cell populations in the brain of intact 15 rats. We failed to find cell groups demonstrating a coexpression of nestin and Msi-1. However, after ischemic lesion of the brain, which was caused in 38 rats by an endovascular occlusion of the left medial cerebral artery for 30 min with the following reperfusion for 48 hours, both markers were detected in cells of subventricular zone and in ependymocytes. These results indicate the changes in cytochemical patterns of the candidate stem cells.

The article presents new approach to treatment of radiation disorders presenting as indolent ulcers. The approach is based on autologous multipotent mesenchimal stromal cells applied locally and injected around the injuried zone. The ulcers heal due to the fact that the transplanted cells stimulate local regeneration processes, angiogenesis, ceased inflammation and apoptosis. The method is a new medical technology based on vast preclinical studies and could be put into medical practice.

Regeneratory activities of Baikal aconite alkaloids were studied on the excision skin wound model. Manifest wound healing effects of songorine, napelline, and hypaconitine were detected. The therapeutic efficiency was based on activation of residual mesenchymal progenitor elements. The development of this phenomenon was explained by the direct effects of alkaloids on precursors and by higher production of growth factors by the skin stromal cells. Songorine exhibited the most pronounced specific activity due to more significant stimulation of progenitor cell differentiation associated with maximum activation of the secretory function of the microenvironment cells.

One of the major directions of development of cell therapy is a therapeutic angiogenesis. Progress in this area is associated with the discovery of endothelial progenitor cells, which play an important role in neovascularization of adult tissues. The list of candidate cells for the regeneration of the cardiovascular system is constantly updated. Nevertheless, these preclinical and clinical studies to assess the possibility of using cells for therapy, isolated from different sources are contradictory. For urgent issues in the research of cell therapy include lack of uniform nomenclature, as well as the lack of functional characteristics expected of stem/progenitor cells. Given the controversial results of initial clinical trials, require more accurate knowledge of the biological properties of cells used for transplantation.