Using the model of alloxan-induced diabetes mellitus on rats we demonstrated the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of the pancreas and normalization of blood glucose concentration. The preparation produced an antiinflammatory and antisclerotic effects associated with activation of stem cells and their determined homing into the pancreas.

to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID).

Chromosome complements of twenty hybrid clones obtained by fusion of Mus musculus embryonic stem cells (ESC) and M. caroli splenocytes were studied. Using of double-color in situ hybridization with chromosome- and species-specific probes we were able to detect the parental origin for each chromosome in hybrid cells. Based on parental chromosome ratio, all 20 hybrid clones were separated in some different groups: from the group containing practically tetraploid M. musculus genome with single M. caroli chromosomes to hybrids with dominance of M. caroli chromosome homologues. In 8 hybrid cells clones we observed prevalence of chromosomes originated from ESC in ratio from 5:1 to 3:1. Another hybrid cells clones have either equal (1:1, 1:2) ratio of M. musculus to M. caroli chromosomes or with the prevalence of ESC- (2:1) or splenocyte- (1:2) originated parental chromosome homologues. In 3 hybrid cells clones, we observed preferable segregation of ESC-originated pluripotent chromosomes. This phenomenon was found for the first time and it possibly indicates compensation of the epigenetic differences between parental chromosomes of ESC- and splenocyte-origination.

The debatable article is devoted to the analysis of consecutive changes of the notion about the origin, migration, morphofunctional heterogeneity, differentiation and proliferative potential of the basic cells of a connective tissue--fibroblasts. Despite of a plenty of an actual material on this section of cellular biology, till now there is no uniform concept about fibroblasts to a full degree defining their cytogenesis, features of phenotypic answers, and position in differon organization. In this article, the data available in literature are systematized and generalized. The modern outline of fibroblastic differon is offered for the subsequent determination of role and place of its various parts in normal physiological and pathological reactions of connective tissue.

Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes. All these data indicate the existence of universal reaction of homological chromosome loci transposition which was revealed during AR development in differentiated (lymphocytes) and non-differentiated (hMSCs) and also it shows possibility of radiational BE development in suspension and monolayer cell cultures upon addition of stress-signalization factors in incubation medium. We suppose that these factors are extracellular genome DNA fragments apoptotic cells.

The expression of genes Sox2, Klf4, Myc, Sall4, Gata6, Foxa2, Hnf4a, Cdx2, Esrrb, Hand1 in cultivated cells, embryos and organs of adult voles Microtus rossiaemeridionalis was studied. High resemblance of the expression patterns of these genes in the organs of adult voles, mice and humans was demonstrated. It was established that genes Gata6, Foxa2 and Hnf4a were specifically expressed in vole extraembryonic endoderm cells, while Cdx2 and Handl genes, in trophoblast stem cells. This shows that these genes can be used markers for corresponding vole cell lines. Indirect confirmation pointing to the fact that Oct4 gene is a marker gene for epiblast cells both in the vole and mouse was obtained.

This review summarizes the data characterizing the effect of ageing on the development of male germ cells and their hereditary structures. We have studied causes of spermatogenesis reduction at late stages of ontogenesis. We have focused on age-specific changes of the structural-functional integrity of stem spermatogonial cells and their microenvironment (niche). We also examined several unique and specific features of the spermatogenic system in senescence-accelerated mutant mice (SAM), with accelerated ageing.

Major technologies of transient and stable transgene expression in hMSC are reviewed. Properties and efficiencies of recombinant lentiviruses, adenoviruses, AAV and baculoviruses used for hMSC transduction are compared. The aims oftransgenesis include directed differentiation of hMSC, function improvement, correction of pathology factors and proliferatrion control, as well as many basic research challenges.

The effect of serotonin on the formation of neurons producing gonadotropin-releasing hormone (GnRH) during embryogenesis of Wistar rats was studied. The neurons producing GnRH were detected immunocytochemically on days 18 and 21 of embryonic development and on day 15 of postnatal development of rats with normal serotonin metabolism and rats in which the synthesis of serotonin was inhibited by p-chlorophenylalanine. The total number of GnRH neurons in serotonin deficiency was larger than in the case of its normal metabolism at all developmental stages studied. This is an indirect evidence for the inhibitory effect of serotonin on the formation ofGnRH neurons. To confirm the morphogenetic effect of serotonin, we studied the rate of formation of GnRH neurons by injecting bromodeoxyuridine in the formation period of these neurons. It was found that serotonin deficiency had no effect on the time of formation of GnRH neurons: over 97% of neurons formed on days 11 to 15 of embryonic development both in the experimental and control groups. Note that, in serotonin deficiency, the maximum number of GnRH neurons formed one day later than in the normal state. Thus, serotonin inhibits the proliferation of GnRH neuron progenitor cells and thereby has a morphogenetic effect on the development of these neurons.

Aim of the study was to assess participation in development of restenosis of circulating in blood progenitor cells of stromal line of differentiation and polymorphonuclear granulocytes. We compared levels of osteonectin positive progenitor cells, neutrophils, eosinophils, and basophils in blood of patients with ischemic heart disease (IHD) in whom according to data of angiographic study after endovascular myocardial revascularization with the help of stents with drug coating (Cypher, Cordis Corp, USA) restenosis was detected (n=15), in patients without restenosis (n=23), and in healthy persons (n=17). Levels of stromal progenitor cells and polymorphonuclear granulocytes in blood were measured with the help of methods of flow cytometry. In groups of patients with IHD with and without restenosis number of osteonectin positive cells in blood was higher than in healthy subjects (2.4+/-0.7 and 2.5+/-0.9 vs 1.5+/-0.5 cells/ microL, respectively, p=0.004) without significant differences between groups (p=0.59). These 2 groups of patients did not differ by numbers of leukocytes, neutrophils, and basophils in blood. At the same time we found that in patients with restenosis number of eosinophils in blood was significantly greater than in the group of patients without restenosis (262+/-68 vs 124+/-67 cells/ microL, respectively p<0.001). Moreover in patients with level of eosinophils exceeding 170 cells/ microL rate of development of restenosis was 74% against 5% in patients with number of eosinophils less than 170 cells/ microL (p<0.001). Thus level of stromal progenitor cells in blood of patients with IHD was higher than in healthy persons and remained equally high in groups with and without restenosis. Number of blood eosinophilic leukocytes in patients who had been subjected to coronary stenting in whom later restenosis developed was significantly higher than in patients without restenosis. The data obtained indicate at the presence of link between development of in - stent restenosis and elevated content of eosinophilic granulocytes in blood of patients with IHD.

The influence of multipotent mesenchymal stromal cells (MMSC), got from allogenic bone marrow, on local radiation injury in rats after beta-irradiation by a source 90Sr/90Y in a dose 140 Gy under various conditions and ways transplantation was studied. It was established, that transplantation MMSC, allocated on biodegradative membranes, which have been carried out for 21 day after an irradiation in conditions minor surgical of ulcers, resulted in reduction of the area of local beam defeats and acceleration of healing of skin, in comparison with the control of an irradiation. The introduction of suspension MMSC subcutaneous around of the center of a defeat at 8 day after an irradiation caused earlier healing of ulcers. It was concluded, that application of MMSC is perspective for treatment of local radiation injury and necessity of development of optimum conditions of their use at cell therapy of radiation injury of skin.

The study was designed to analyse results of alternative methods of myocardial revascularization in "no-option patients" to whom direct revascularization is not indicated. Over 600 cases were treated with the use of transmyocardial laser revascularization (TMLR), angiogenic factors (VEGF, alpha-ECGF), and cellular therapy. It was shown that TMLR is a safe and efficacious procedure increasing perfusion and normalizing myocardial metabolism. It eliminates angina and improves quality of life of the patients. Single bolus administration of angiogenic factors alone does not stabilize perfusion and patients' condition. The use of stem cells provokes the growth of new vessels and promotes restoration of viable myocardium via stimulation of angiogenesis. However, mesenchymal stem cells do not contribute to scar reparation and are inefficient in patients with a critical mass of cicatrically-altered myocardium.

Cell therapy is a modern and promising approach to type I diabetes mellitus treatment. Nowadays a wide range of cells is used in laboratory experiments and clinical studies, including allogeneic and xenogeneic cells of Langergance islets, bone marrow cells, haematopoietic stem cells, mesenchymal stem cells, and cord blood stem cells. Any type of the cells named could correct the status of the patients to a certain extent. However, full recovery after cell therapy has not been achieved yet.

Leukemia is a clonal proliferative disorder of the multipotent hematopoietic stem cells that leads to abnormal cell growth and (or) differentiation. The hallmark of the disease is the presence of oncogene expression in bone marrow or peripheral blood as a result of some chromosome translocations. The development of leukemia with transfer to disease progression presents a multistage process implicating series of molecular changes leading to chromosomal instability and aneuploidy. The most possible of these changes include the followings: appearance of additional chromosome translocations, activation of other not previously expressed oncogenes, loss of tumor suppressor genes, abnormal centrosome duplication, and dysfunction of the genes which coordinate the accurate chromosome alignment and chromosome segregation during mitosis. The two latter molecular changes which are controlled by mitotic spindle checkpoints play the role in leukemogenesis and are probably involved in apoptosis.

Presented herein are the outcomes of using autologous progenitor cells of the bone marrow in a total offorty-two male patients suffering from atherosclerosis obliterans of the lower-limb arteries with degree II B of ischaemia according to the classification of A. V. Pokrovsky, preconditioned by involvement of the femoropopliteal-tibial segment with no possibility to perform a reconstructive operation. It was a randomized, double-blind, placebo-controlled study limited by a clinical approbation of the method concerned. Bone marrow was sampled from the crests of the iffac bone. Exflisate was subjected to double centrifugation to obtain the leukocytic fraction of the bone marrow, immune magnetic separation--for obtaining the CD 133+ cells. The patients were subdivided into three groups, each consisting of 14 subjects. Group One patients received autologous progenitor cells CD133+, Group Two patients were given the leukocytic fraction of the marrow (CD34+), and Group Three patients (comparison group) received normal saline as aplacebo. The preparations were administered into the muscles of the internal and external surface of the crus. The clinical outcomes were evaluated according to the Rutherford scale and demonstrated that Group One and Group Two patients given the cellular material exhibited a statistically significant improvement of their clinical condition, as compared with the findings obtained in the placebo group (P < 0.001, by the Mann-Witney test). Based on the results of the treadmill tests performed after 1, 6 and 12 months, the distance of pain-free walk was noted to statistically significantly increase in Group One and Group Two patients, as compared with those from the placebo group. The proposed method of treatment may be recommended for multicenter clinical trials.

Use of synthetic osteoplastic materials not always leads to formation of the necessary bone tissue volume. The alternative high technological implantation material can become tissue engineering constructions containing osteogenic precursor cells. Clinical observation of sinus lifting with the use of tissue engineering construction demonstrates the efficacy, shortening the terms of operation wound healing, young bone tissue formation after transplantation and possibility to install implants already after 3 months if the amount of bone is sufficient for primary fixation.

The compensative effects of gravitation at the first stages of embryonic development stages have been investigated using slow clinorotation of embryoid bodies from mouse R1 stem cell lines. Semithin sections (1-2 microm) analysis and electron microscopy study of embryonic bodies cells allowed to reveal morphological features of cells at different maturation stages. Significant decrease in the number of embryonic stem cells undergoing apoptosis as well as noticeable reduction of "lacunas" relative areas were found in clinorotated embryonic bodies compared to control. We propose that large cyst absence may be caused by initial differentiation and morphogenesis stages delay associated with autophagy processes in embryonic bodies.

Cytoskeletal alterations occur is several cell types including lymphocytes, glial cells, and osteoblasts, during spaceflight and under simulated microgravity (SMG). One of the potential mechanisms of cytoskeletal gravisensitivity of a cell is disruption of extracellular matrix and integrin interactions. Therefore, we investigated the effects of SMG on F-actin cytoskeleton structure, vinculin focal adhesions, expression of some integrin subtypes and cellular adhesion molecules in mesenchymal stem cells (hMSCs) derived from human bone marrow in vitro. Simulated microgravity was produced by RPM (manufactured by Dutch Space, The Netherlands). Culture flasks with MSCs were settled on the inner platform of RPM for 30 minutes, 6, 24, 48 and 120 h. The results have shown that actin cytoskeleton is very fast reorganized even after 30 minutes of simulated microgravity. The number of cells with disrupted actin cytoskeleton steadily increased with the increasing exposure time. However these changes were reversible because the cells partly recovered their F-actin structure after 120-hours-exposure. In addition, we observed vinculin redistribution inside the cells after 6 hours and subsequent terms of exposures. This process was accompanied with increasing of fluorescence intensity of cells. The expression of integrin-alpha2 increased after exposure in RPM. Also we observed decrease in the number of VCAM-1-positive cells and changes in the expression of ICAM-1. Thus, our findings indicate that SMG leads to reversible microfilament alterations of hMSCs and alters adhesion properties of this type of cells.

The melatonin effect on the anterior and posterior ends of a free-living flatworm Girardia tigrina was studied, as well as the variability of the mitotic activity of the stem cells (neoblasts) in the anterior and posterior postblasteme. This hormone may inhibit the regeneration of the anterior end of the animal in the physiologic-friendly concentrations of 10(-10)-10(-15) M by suppressing the mitotic activity of the neoblasts. This hormone does not affect the posterior end's regeneration; thus, its regeneration effect is significantly elective.

The effect of retinoic acid on regeneration of two species of asexual planarian races, Girardia tigrina and Schmidtea mediterranea, was studied. It was established that retinoic acids at physiological concentrations (10(-7)-10(-10) M) inhibit the regeneration of the head part of planarians but have no effect on tail blastema growth. It is shown that regeneration of the head part is inhibited as a result of arrest of the cell cycle of neoblasts, proliferating stem cells, during the transition from the G1/G0 to the S phase. Thus, the morphogenetic role of retinoic acids in planarians, primitive bilaterally symmetrical animals, has been demonstrated.