Changes in the capacity of hemopoietic stromal microenvironment to promote homing of hemopoietic stem cells from different hierarchical compartments were evaluated in mice treated with parathyroid hormone by determining their 24-h precipitation factor. This parameter did not change for splenic short-living hemopoietic stem cells (splenic CFU) and considerably decreased for the bone marrow of mice treated with parathyroid hormone. For earlier long-living hemopoietic stem cells (cells forming the cobblestone area on day 28) the precipitation factor after injections of parathyroid hormone did not change in the bone marrow and decreased in the spleen. These data suggest that parathyroid hormone decreases the efficiency of homing of short-living hemopoietic stem cells in the bone marrow.

We studied the role of monoamines in the regulation of functional activity of granulocyte-macrophage precursors during neuroses. Under conditions of conflict situation and paradoxical sleep deprivation, monoamines of the central nervous system regulate proliferation and differentiation via alpha-adrenergic structures on granulomonocytopoietic precursors and cells of the hemopoiesis-inducing microenvironment.

Effects of randomized gravity vector (clinostatting) on embryonal stem cells (ESC) of mice were evaluated in vitro with respect to proliferation, proliferative potential, and differentiability. Colony formation remained normal up to hour 72 of clinostatting; however, further exposure led to fusion of the ESC colonies. No reliable shifts in the proliferative activity were found, whereas morphometric analysis showed different dynamics of the ESC colonies size in specific periods of the experiment comparing with the control. Evaluation of the ESC proliferative potential after the experiment revealed a trend upward in the number of colonies when compared with the dynamic and static controls. However, the number of resulted EBs in the control tended upward contrary to EBs formed under the conditions of clinostatting and continuous agitation pointing to the importance of local medium conditioning at the beginning of ESC differentiation.

This paper presents the critical analysis of the data published in recent literature, which concern the role and significance of stem cells (embryonic stem cells and progenitor cells) in the processes of reparative morpho- and histogenesis in the different animal and human organs. Possible negative effects of the application of stem cells for the stimulation of reparative histo- and organogenesis are discussed. Special attention is drawn to the necessity of more cautious and balanced approach to the use of stem cells for stimulation of repair processes in the organism.

The aim of this study was to develop an optimal and easy protocol for immunocytochemical demonstration of nestin (an intermediate filament protein which is believed to be a neuronal stem cell marker) in paraffin sections of rat brain with target retrieval procedure being omitted for better preservation of the neural tissue structure. The influence of fixation, character of blocking of nonspecific antibody binding, temperature and time of incubation on the results of immunocytochemical reaction was studied. On the basis of the results obtained, we propose a processing protocol allowing distinct demonstration of nestin in rat brain cells together with the optimal preservation of the nervous tissue structure.

Review of ethical issues related to the application of embryonic steam cells (SC) for the treatment of different diseases is presented. On the background of ethical considerations, limits and possibilities as well as advantages and shortcomings of using steam cells in the clinical practice are discussed. On the basis of analysis of scientific reference data and ethical side of the given issue, it may be concluded that the principle "don't harm" must be applied also and especially for the use if this particular type of treatment in the clinical practice.

The review describes the role of positive and negative feedback released through end-products of erythroid cells in the regulation of erythropoiesis.

Quantitative and qualitative chromosome rearrangements in the cell line G1 established from a genital ridge of the 12,5 dpc BALB/c mouse embryo were analysed. Cytogenetic analysis was performed on the 75th passage of in vitro cultivation. It has been shown that by this passage the cell population was heterogenous. It is suggested that such heterogeneity may be caused by realization of two simultaneous processes namely the cell polyploidization and their secondary diploidization. These processes were accompanied by some chromosome destructions, and the creation of small new acrocentric chromosomes and large aberrant chromosomes as well as Robertsonian translocations. The present study demonstrates in vitro karyotype evolution of the mouse cell line G1 including the increased instability of the chromosome apparatus.

The results of clinical studies dedicated to treatment with stem cells and other cell technologies were analyzed from the position of evidence-based medicine. Literature data on the safety of cell therapy and the effectiveness of new treatment technologies were summarized according to systems and organs. Cell therapy is becoming more and more applicable to clinical practice in patients with all groups ofpathology. Its safety and effectiveness has been proved in principle, although there are no affirmed algorithms. The authors formulate the main principles of further clinical investigations and substantiate the necessity to conduct research according to blind randomized protocols, which allow meta-analysis.

The sensitivity of stromal stem cells (CFU-f) from rat bone marrow and fetal liver to the cytotoxic effect of 5-fluorouracil (5-FU) was compared in vivo and in vitro. Cells from both tissues demonstrated a similar resistance to 5-FU in vitro; however, stromal stem cells from fetal liver proved notably more sensitive to 5-FU compared to marrow CFU-f in vivo. Cells forming colonies of different size were identified in stem cell populations from both tissues. Cells giving rise to small colonies had a higher resistance to 5-FU both in vivo and in vitro.

Epidermal human cells (keratinocytes) differently interact with extracellular matrix proteins of the skin basal membrane depending on the stages of their differentiation. The pool of basal keratinocytes commonly includes stem cells and transient amplifying cells. They directly attach to the skin basal membrane. Keratinocytes change their adhesive properties during differentiation, lose direct interaction with the basal membrane and move to suprabasal epidermal strata. From this, it is suggested that basal and primarily stem cells can be isolated from a heterogenous keratinocyte population due to their selective adhesion to the extracellular matrix proteins. In the current study, we analysed the specificity of interaction between primary keratinocytes and extracellular matrix proteins (collagens of I and IV types, laminin-2/4, fibronectin and matrigel). We have demonstrated that the basal keratinocytes extracted from the skin have different adhesive abilities. The rapidly spreading cells usually interacted with collagen and fibronectin rather that with laminin-2/4 or matrigel. The majority of these cells being represented by basal keratinocytes. Our data demonstrate that the applied method of keratinocyte selection may be directed for precise isolation of skin stem from a common cell population.

Data published on the use of cytokines for the stimulation of neoangiogenesis and cardiac regeneration have been systematized. There is evidence that insulin-like growth factor (IGF1) can stimulate proliferation of cardiomyocytes; hepatocyte growth factor (HGF) does not influence the mitosis of cardiac cells, but prevents post-infarction remodeling of heart; vascular endothelial growth factor (VEGF) stimulates proliferation of endothelial cells in vitro and neovasculogenesis in the ischemic heart in vivo for both animals and humans; fibroblast growth factor (FGF) can also induce neovasculogenesis in the ischemic heart; granulocyte-colony-stimulating factor (G-CSF) can mobilize stem cells and endothelial progenitor cells in bone marrow, which are involved in neoangiogenesis and cardiac regeneration; erythropoietin can mobilize endothelial progenitor cells from bone marrow and induce neovascularization of ischemic tissue in vivo. It is suggested that VEGF, G-CSF and erythropoietin are the most promising compounds for the stimulation of neoangiogenesis and cardiac regeneration in patients with myocardial infarction.

The influence of ginseng and skullcap (Scutellaria baicalensis) extracts on the local mechanisms of erythropoiesis control under the conditions paradoxical sleep deprivation has been studied. The regulatory action of both preparations on the bone marrow erythropoiesis is based on their ability to influence the proliferation and differentiation in erythroid cells-precursors via modulation of the functional activity of cellular hemopoiesis-inducing microenvironment elements. In particular, the drugs induce changes in the structural and functional organization of the bone marrow and in the production of short-range humoral erythropoiesis regulatory elements.

The effect of histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butirate (NaBut) on the proliferation of murine embryonic stem cells (MESC) was studied. Both agents suppressed the population growth and clonability of MESC. Flow cytometry analysis showed a decrease in the amount of S-phase cells upon treatment with HDAC inhibitors. TSA treatment caused a decrease in mRNA level of such positive cell cycle regulators as cyclins D1, A, c-myc, cdc25A, and induced transcription of negative regulators of the cell cycle--p21(Wafl) and p57(kip2). Also, HDAC inhibitors decreased the level of e2f-dependent transcription, with the concominant reduction of mRNA level of e2fl gene. HDAC inhibitors also affected the survival of MESC. A 2 day TSA treatment resulted in massive detachment and cell death, as confirmed by DNA laddering and MTT assay. Treatment with TSA for 2 and 5 days did not induce SAPbetaGAL, activity and p16(ink4a) transcription, i.e., characteristic features of senescent fibroblasts. In summary, HDAC inhibitors decrease the rate of proliferation affecting cell cycle and viability of MESC. We conclude that MESC are unable to realize a sustainable block of the cell cycle upon treatment with HDAC inhibitors.

The kinetics, proliferation and differentiation potentials of hemopoietic stem cells (CFUs) of bone marrow and spleen were investigated in CBA-line mice in the early period (1-30 days) of chronic gamma-irradiation at a dose rate of 0.16 Gy/day to attain a cumulative dose of 4.8 Gy. The results of the experimental study showed the prevalent maintenance of productivity of granulocytic and erythrocytic hemopoietic cell series within the range of reference values, persistent inhibition of the megakaryocytic series (in terms of all hemopoiesis parameters of interest), more marked suppression of the population of polypotential CFUs in the bone marrow as compared with that in the spleen. The obtained results indicated that the mechanisms of hemopoiesis compensation at stem cell pool level were as follows: the increase in proliferation potency of erythrocytic and in polypotential precursors, the rise in the proportion of granulocytic precursors in the real differentiation potential of CFUs, and the processes of repopulation manifested with different intensity in all stem cell populations under study. For maintenance of the necessary productivity of CFUs in each of hemopoietic cell series, consecutively or simultaneously, several compensatory-adaptive mechanisms are started, which allows the avoidance of a sharp competition between hemopoietic cell series under the conditions of stem cell pool depopulation, and preservation of the hemopoiesis as a whole.

The parameters characterizing the state of hemopoietic cells obtained from chronically exposed residents of the Techa riverside villages studied at late time after the exposure included: the level of somatic mutations in the TCR gene, the level of chromosome aberrations, the intensity of peripheral blood lymphocyte apoptosis. Exposed versus unexposed subjects (controls) showed an increased frequency of CD3-CD4+ T-lymphocytes, chromosome aberrations of stable type (translocations) and unstable type (dicentrics, rings), and also increased intensity of lymphocyte apoptosis. The findings of tests using a standard additional gamma-irradiation (1 Gy) accompanied by 24-hour incubation indicated that the rate of apoptosis of lymphocytes was significantly higher in exposed individuals in comparison with unexposed ones. It was suggested basing on the obtained data that at late time the chronic (for over 50 years) exposure at RBM doses from 0.01 to 3.22 Sv was a factor inducing the damage to the genetic apparatus of hemopoietic cells. Evidently, the initial chronic low-intensity irradiation in the above-indicated dose range activates adaptive processes at the cellular level in hemopoietic cells. Late time after the onset of exposure the adaptation reserves are depleted in chronically exposed persons which brings about its failure in the case of a challenge by additional external exposures.

The authors have analyzed their experiences with treatment of 50 patients with ischemic heart disease using transplantation of autologous mono-nuclears of the bone marrow. It was shown that this operation resulted in an improvement of indices of the heart functions and myocardium metabolism. Transplantation of stem cells as mononuclear fraction of the bone marrow is indicated in treatment of different groups of patients: in recurrent diseases after previous operations on the coronary arteries; in patients with distal lesions of the coronary bed; transplantation of autologous stem cells of the bone marrow is expedient simultaneously with coronary artery bypass grafting or coronary angioplasty (stenting).

This review presents the systematized summary of classical and current conceptions on the functional morphology of the surface epithelium of esophageal tunica mucosa. The data describing the architecture of epithelial lining, classification and structure of its layers, are presented. The detailed characteristics of the cells of each layer and their ultrastructure, organization of germinal compartment, stem cell distribution and activity as related to their topography, are presented. The parameters of epitheliocyte cell cycle, mechanisms controlling their proliferation and circadian rhythms by growth factors and hormones, changes of proliferation activity under natural, pathological and experimental conditions, are discussed. The process of epithelial desquamation is described, as well as a mucus layer covering the epithelial surface together with its sources and protective role. The characteristics of the process of epitheliocyte apoptosis and the mechanisms of its control in normal and pathological states, are presented.

Murine embryonic stem (mES) cells can proliferate independently of the presence of growth factors in the medium. It is yet unknown what intrinsic activity triggers cell cycle events in mES cells. Here we investigated the contribution of the PI3-kinase cascade to autonomous proliferation of mES cell using PI3-kinase inhibitors wortmannin and LY294002. Wortmannin displays a weaker inhibitory effect on phosphorylation of PI3-kinase pathway target PKB as compared with LY294002, and does not downregulate mES cells proliferation, while LY294002 causes a strong decrease in the share of cells in S-phase and accumulation of cells in G1 phase. Both inhibitors cause significant decrease in cyclin D1 amount. The treatment with LY294002, rather than with wortmannin results in a decrease of cyclin E amount and cyclin E-assossiated kinase activity. In mES cells, inactivation of PI3-kinase-dependent pathway and G1 arrest are not accompanied by induction of p27kip 1 transcription and accumulation of this inhibitor of cyclin-cdk complexes at the protein level, implying that these events accomplished by some p27kip 1-independent mechanism. Both LY294002 and wortmannin cause apoptotic death of mES cells and downregulate the growth of population. Thus, inactivation of PI3-kinase in mES cells may lead to apoptosis rather than to cell cycle arrest.