Gene function disclosure and the development of modern technologies of genetic manipulations offered the possibility of genetic reprogramming application to alter cell specialization. With the involvement of a gene set that encodes the transcription factors responsible for the pluripotent state, any cell of an adult body could be reprogrammed into the embryonal.state and pluripotency could be induced in this cell. Such reprogrammed cells were called induced pluripotent stem cells (iPSCs), and they are capable of again passing through all developmental stages. This provides new possibilities for studies of the basic mechanisms of developmental biology, the formation of specific cell types, and the whole body. In culture, iPSCs could be maintained permanently in a nontransformed state and permit genetic manipulations while maintaining their pluripotent properties. Such a unique combination of their properties makes them an attractive tool for studies of various pathologies and for the delineation of treatment approaches. This review discusses the basic and applied aspects of iPSCs biology.

Short (25-35 nucleotides) regulatory piPHK, along with RNA-binding proteins of the Piwi family, constitute an evolutionarily conserved system that functions mainly in eukaryotic gonads. The system can be regarded as a variant of the mechanism of RNA interference, which is based on the recognition of target RNA as a result of complementary interactions with piRNA. The variants of this regulatory system function in the germline cells, including stem cells and somatic cells of the niche, ensuring maintenance of the germline stem cells and their differentiation. One of the most important functions (but not the only one) of this system is the repression of transposons, which guarantees genome stability in germline cells. This review focuses on the works of the authors of the review in the context of outstanding international achievements in a rapidly evolving re- search area, the biology of piRNA and the function of the Piwi protein.

Cancer stem cells (CSCs) possess self-renewal and heterogeneous cancer cell lines formation. Numerous data confirm the existence of a model in which CSCs have an important role in cancer initiation, progression and clinical outcome. Analysis of CSCs role in metastasis, in contrast, remains mainly conceptual and hypothetical. Recent data are summarized in this review which support the CSCs theory as a source of breast cancer metastatic lesions with noting the key role of the microenvironment.

The objective of the present study was to review the experimental studies concerned with in vitro and in vivo visible and infrared light irradiation of human and animal stem cells (SC) to assess the possibilities of using its photobiomodulatory effects for the purpose of regenerative medicine (RM). Despite the long history of photochromotherapy there is thus far no reliable theoretical basis for the choice of such irradiation parameters as power density, radiation dose and exposure time. Nor is there a generally accepted opinion on the light application for the purpose of regenerative medicine. Therefore, the clinical application of light irradiation remains a matter of controversy, in the first place due to the difficulty of the rational choice of irradiation parameters. In laboratory research, the theoretical basis for the choice of irradiation parameters remains a stumbling block too.

Multipotent mesenchymal stromal (stem) cells (MSCs) are a heterogeneous cell population of different commitment and is actively involved in the physiological and regenerative tissue remodeling. MSC mobilization from local tissue depots and their activation in the tissue damage foci are the key issues in the study of mechanisms of MSC features. Short-term (up to 72 h) hypoxic stress that is considered as a constitutive feature of the damage foci, may contribute to the activation of MSC potential. This review is analyzed the data on the impact of short hypoxic stress ex vivo on the viability, functional activity of MSCs and possible molecular mechanisms of these effects.

Buffy coat samples containing lymphocytes, monocytes and granulocytes, were obtained from the peripheral blood of 16 donors who had clinical manifestations of atopic hypersensitivity in their medical background. After ex vivo incubation with donor-specific allergens, the percentage of B- and T-lymphocytes and natural killers (NK) remained unchanged. Buffy coat incubation with allergens induced production of IgE and IL-4 in all studied samples. In 13 out of 16 cases the reaction to contact with an allergen was also evident in the increasing of T-activated lymphocytes (CD3+, HLA-DR+) subpopulation. Co-cultivation with MSC from bone marrow, adipose tissue and umbilical cord resulted in blocking of allergen-induced IgE and IL4 secretion and HLA-DR+ T-lymphocytes subpopulation increase. There were no significant differences in the effect of MSCs, isolated from three different sources, on allergen-specific responses of leukocytes. Co-culturing of leukocytes with MSCs from all three sources led to an increase in the content of regulatory T-lymphocytes by an average of 30%. Thus, the immunomodulatory activity of MSCs in vitro results in blocking of the effector part of allergic reactions.

One of the important questions in understanding the mechanisms of carcinogenesis induced with foreign body (or plastic carcinogenesis), is a question about normal progenitor cells in sarcomas (FB sarcomas) appearing in close proximity to the plastic plate implanted under the skin of an experimental animal. There is an assumption in literature that progenitor cells in FB sarcomas originate from vascular endothelium cells feeding a connective tissue capsule that forms around foreign body. In our research, we studied mRNA expression of one of the endothelial cell markers--receptor VEGFR2/FIk1--and growth factor VEGF-A, which interacts with it, in precancerous cells of FB sarcomas in mice. In examined cells, mRNA expression of VEGF-A was found while mRNA expression of VEGFR2/FIk1 was absent. In light of this and formerly established properties of progenitor cells in FB sarcomas, possibilities of the origin of these sarcomas from endothelial cells, pericytes, and pluripotent mesenchymal stem cells are being discussed.

Studying mesenchymal stromal cells (MSC) is a very topical problem. Numerous experiments in vitro promoted understanding of MSC biology to a great extent. However, many aspects of their behavior in vivo still remain unclear. This review deals with MSC localization and functioning in an organism. MSC are present in various tissues, changing their numbers and traits during ontogenesis. Pericytes, or adventitial cells, can be considered as possible equivalents of MSC in vivo. Self-maintenance, proliferation, and differentiation of MSC are controlled by their tissue microenvironment that includes surrounding cells, soluble molecules, and extracellular matrix. At early stages of ontogenesis, MSC, probably, migrate throughout an organism. The migration occur also through a mature organism when tissues happen to be damaged. MSC move pointedly to the damaged parts and render a reparative effect which is due, first of all, to paracrine production of bioactive molecules. Immunomodulatory properties of MSC also play their role in tissues regeneration. An important function of MSC consists in creation of hematopoietic microenvironment. They secrete humoral regulators of hemopoiesis such as cytokines and chemoattractants. In addition, they interact with hemopoietic cells via surface molecules. Possibly, MSC sustain the stable functioning of other tissues as well. Their unique features make them quite attractive for clinical use, although successful introduction of MSC into medical practice requires their further studying.

Adult corneal epithelium is often exposed to environmental stress, injured and repaired by limbal stem cells. Injury of corneal epithelial layer leads to reduction of visual clarity and loss of vision. Recently it was shown that epithelial layer also contains stem cells. Obtaining cell culture of corneal epithelium will allow understanding mechanisms of cell behavior and differentiation, their metabolism and reaction on environmental stress in health and disease. Moreover, cultured corneal epithelial cells can be considered as a promising material for constructing bioartificial cornea. The aim of this study was to isolate cells of anterior corneal epithelium from human donor cornea and to study their morphological and functional characteristics in vitro. The results of our study showed the possibility of culturing epithelial cells in vitro. The observed changes in cell morphology, their flow growth character as well as active proliferation and up-regulation of mesenchymal markers expression, indicate, in our opinion, epithelial-mesenchymal transition taking place in long-lasting culture of human anterior corneal epithelial cells. The obtained cultures can be used for further studies of pathological processes taking place in cells during drugs testing or controlling the phototoxic effect of different types of emission.

The paper presents an overview of cellular therapy products and medical tissue engineering of the leading countries of the world (including the US) and identifies lines of research in the field of cellular technology application in the interests of national military medicine. The authors gave information concerning practical implementation of the achievements of biomedical research in the field of regenerative cellular products and technologies in Russia as different products, which may be used at the stages of medical evacuation. The authors presented results of research, which was, performed on the model of mine blast injury in accordance with principle possibility of the usage of cellular technologies products (multipotent mesenchymal stromal cells) in medical practice.

Nuclear receptors (NRs) are ligand-activated transcription factors that play an important role in metabolism, homeostasis, differentiation and development regulation. NRs are also involved in pathogenesis of various diseases. For most of NRs natural ligands are known. Ligand-activated NRs bind specific nucleotide sequences in target genes and induce their expression. DAX1 protein is an unusual member of NR superfamily that does not have ligand and lacks typical DNA-binding domain. It was established 20 years ago that DAX1 plays a critical role in regulation of adrenal and gonadal development and in biosynthesis of steroid hormones, however the molecular mechanisms of its action remained not fully understood. Further studies have shown that this piotein can interact with many members of NR superfamily and with different co-repressors and co-activators of transcription. Its functions are not restricted to regulation of adrenal and gonadal development and steroidogenesis. Recent studies have elucidated the role of DAX1 in pathogenesis of X-linked adrenal congenital hypoplasia and dose-sensitive sex reversal. It was found also that DAX1 is an important component of transcription factors network that maintains the pluripotency of mouse embryonic stem Cells. Here we review the current knowledge on properties, functions and mechanisms of DAX1 action. The role of DAX1 in pathogenesis of inherited diseases is discussed. The specificity of DAX1 interaction with various protein.partners is characterized. The examples of co-repressor and coactivator action of DAX1 on transcription are presented. The potential association of DAX1 with oncoendocrine pathologies and its role in self-renewal of mouse embryonic stem cells are described.

The paper described a new mutation that causes the development of multiple meristematic foci as part of shoot apical meristem, which can give rise to new stem axes or cause stem fasciation. The wus-1 mutation represses development of additional apical meristem in fas5 mutant, indicating to the sequential action of the genes in the formation of the shoot apical meristem and FAS5 gene participation in spatial restriction of the WUS gene expression. This function gene FAS5 performs independently of other negative regulators of WUS gene--namely genes CLV, as demonstrated by additive phenotype of double mutants fas5 clv2-1 and fas5 clv3-2. Besides the effect on the development of the shoot apical meristem fas5 mutation causes a change in the shape and number of leaves, accelerates the plant transition to the reproductive stage and leads to the development of cell neoplasms on the stem (buds, stigmatic tissues and ovule-like structures). The mutation also causes changes in apical meristems and leaf cell morphology indicating the activation in cells of DNA endoreduplication. Pleiotropic effect of the fas5 mutation on different stages of ontogeny and different organs suggests that the FAS5 gene plays a complex regulatory role at all stages of the A. thaliana shoot development, and affects many direct or indirect target genes.

The present article was designed to overview the experimental studies of visible and infrared light irradiation of human and animal stem cells (SC) in vitro and in vivo for the evaluation of its photobiomodulatory effects. The results will be used to elaborate substantiation for the choice of the parameters of SC light irradiation and to develop recommendations for the application of this method in regenerative medicine (RM).

Mesenchymal stromal cells (MSC) represent a heterogeneous population of cells that differ in morphology, phenotype, ability to grow and differentiate, and other properties. Differences between MSC are related in part to the influence of their microenvironment. However, the heterogeneity of these cells also is due to their parent-progeny relationship. Hierarchical organization of the MSC population that comprises different categories of oligopotent and multipotent cells, is complicated and poorly understood. This review includes data on morphological, phenotypic and functional heterogeneity of MSC and its possible connection with the population structure.

Genome editing systems based on site-specific nucleases became very popular for genome editing in modern bioengineering. Human pluripotent stem cells provide a unique platform for genes function study, disease modeling, and drugs testing. Consequently, technology for fast, accurate and well controlled genome manipulation is required. CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPR-associated) system could be employed for these purposes. This system is based on site-specific programmable nuclease Cas9. Numerous advantages of the CRISPR/Cas system and its successful application to human stem cells provide wide opportunities for genome therapy and regeneration medicine. In this publication, we describe and compare the main genome editing systems based on site-specific programmable nucleases and discuss opportunities and perspectives of the CRISPR/Cas system for application to pluripotent stem cells.

Tissue engineering as applied to urologic pathology is covered extremely poor in the literature despite recently gaining popularity of regenerative medicine. The review reflects the current problems associated with reconstructive surgery of the urinary bladder, experience of the researchers from the United States in implementing cellular technologies for bladder replacement, the problems and prospects of this direction in case of such a severe pathology, as fibrous transformated bladder.

The paper gives general information about the epithelial-mesenchymal transition (EMT), its morphological manifestations, altered expression of a number of proteins, types of EMT, and its role in embryogenesis and human diseases, including that about EMT as a mechanism by which the tumor cell acquires prometastatic potential. EMT is a process that is essential in health for gastrulation and the formation of neural crest cells; however, it is also important for the development of abnormalities, among other processes, organ fibrosis and tumor metastases. An understanding of the role of EMT in cancer spread has led to active studies of the process in the past decades. Despite the fact that there are sufficiently many publications on different aspects of EMT, the exact mechanisms regulating the process and the possibility for its therapeutic exposure remain unclear. There is also evidence on the possible association of EMT with the generation of cancer stem cells in tumors.

Experimental data on the presence of immunomodulatory activity, colony-stimulation and radioprotective properties of the polysaccharide from Heliantnus tuberosus L. with the molecular weight of 1-2 MDa, were obtained. The effect of different concentrations of the polysaccharide on production of TNF-α, IL-1β and IL-6 was studied. The nature of radioprotective properties of the polysaccharide is discussed: stimulation of growth of colonies of hematopoietic stem cells, direct interaction with the products of ionizing radiation, and stimulation of cytokine cascades. The possibility of further usage and studying of the polysaccharide is discussed.