The paper reviews research results of myogenic potential, specific properties, functions, and phenotypic features of a number of stem cells populations of muscle and non-muscle origin, their ability to participate in the restoration of the physiological homeostasis of skeletal muscle. The results of scientific research allow to predict with high probability the establishment of an effective cell technology to treat degenerative muscle diseases.

To conduct a comparative study of the structural organization of internuclear interneurons involved in the metabolism of nitrogen monoxide, hydrogen sulphide and carbon monoxide in the caudal brain stem humans.

The transformation of normal precursors into cancer cells is an intricately regulated, multistep process. The master regulatory genes that play a crucial role in the process of organism development may also play a key role in carcinogenesis. From such a point of view, cancer is not simply a genetic disease that is due to a progressive accumulation of mutation--it is also a disorder of the developmental system of the tissue in which cancer emerges. Master regulators and their genes disturb stem cell differentiation upon mutation and thus may serve as targets for cancer therapy, in addition to the classic oncogenes and suppressors of tumor formation. This review is an attempt to give a modern concept of master genes and their functions in adult stem cells of the organism and in carcinogenesis, with pancreatic cancer as an example.

To study the impact of the genes of donor killer cell immunoglobulin-like receptors (KIR) and HLA-KIR ligands on overall (OS) and event-free survival (EFS) rates in patients with myeloid leukemia after transplantation with allogeneic hematopoietic stem cells (allo-HSCT) from HLA-identical related and HLA-compatible unrelated donors.

The effects of fetal calf serum (FCS) growth factor concentration and cell growth phase on production of angiogenic mediators by mesenchymal stromal cells (MSCs) at different O2 levels (20 and 5%) was studied. For this purpose vascular endothelial growth factor (VEGF-A) production was measured in MSC-conditioned medium (CM); besides, branching vessels as well as vessel end points (ramification) in the chorioallantoic membrane of Japanese quail eggs (Coturnix coturnix japonica) were counted following MSC-CM application. During the standard cultivation (20% O2; 10% FCS) the total number of vessels was 1.6 times higher comparing with hypoxic condition (5% O2; 10% FCS) due to increase in ramification, the number of branching vessels did not change. Maximal (double) increase in the total vessel number was observed when CM from MSCs after hypoxia plus serum deprivation was added. VEGF-A synthesis linearly increased with FCS concentration both at 20% and 5% O2. In all cases VEGF-A level was higher at hypoxia. No direct correlation between the VEGF-A concentration and total number of vessels was noted indicating that hypoxia possibly stimulates synthesis of additional angiogenic factors to enhance vascular growth despite the drastic serum deprivation. At 20% oxygen, exponentially growing MSCs showed the highest angiogenic activity and the ramification increased in 1.6 times. Depending on O2, MSCs produced angiogenic factors required at different stages of vascularization. Specifically, mediators of ramification were accumulated in the standard conditions (20% O2) and factors stimulating growth of branching vessels--in hypoxia.

The HLA-typing was carried out concerning of 200 residents of Novosibirsk, potential donors of hematopoietic stem cells on loci (HLA)-A, -B, -C, -DRB1. The study detected in mentioned population two new alleles non-registered previously by the WHO International Committee on nomenclature of factors of HLA-system. The analysis of distribution rates of HLA-alleles and haplotype revealed 16 alleles alternatives of locus HLA-A, 24-HLA-B, 13-HLA-C, 13-HLA-DRB1. The rate of frequency more than 10% is intrinsic to following allele alternatives: HLA-A*02 (29.25%), 01 (14%), 03 (13.5%), 24 (10.75%), HLA-B*35 (12.25%), 07 (12%), HLA-C*07 (29.75%), 06 (13%), 04 (12.5%), 12 (11.5%), 03 (10.75%), HLA-DRB*13 (15.25%), 07 (13.75%), 01 (13%), 11 (12.75%), 15 (12.75%), 04 (10.5%). The application of software Arlequin v. 3.1 established 239 possible gaplotypes HLA-AB-C-DRB1. The gaplotypes A*01-B*08-C*07-DRB1*03, A*02-B*13-C*06-DRB1*07, A*03-B*35-C*04-DRB1*01 with rate of frequency 4.5; 2.75 and 2,75% correspondingly. The The distribution of alleles and analysis of galotypes permitted to compare analyzed population with other Russian populations.

Cancer stem cells may be a source of malignant tumors as well as their relapses after treatment and metastases. They share many features with normal tissue stem cells but also possess mutations and other genetic and epigenetic changes that make them tumorigenic and resistant to conventional cancer therapies. The source of cancer stem cells is discussed: they may originate from normal tissue stem cells as a result of their mutations or deregulation of signaling pathways or alternatively from differentiated tumor cells as a result of dedifferentiation during tumor development. Cancer stem cells reside in a special tumor microenvironment (niche) that regulates their functions. A number of signaling pathways and molecules participate in regulating cancer stem cells features. And although there are some inconsistencies concerning cancer stem cells, their existence may change our view on cancer progression and help to develop new strategies of cancer treatment.

In recent years, engineering of blood vessels, which can provide the effective transport of nutrients and various metabolites, is one of the major challenges in tissue reconstruction. Many researches are carried out to develop cell-seeded bioconstructs based on natural polymers, particularly on PEGylated fibrin. Therefore, the aim of this study was to reveal the optimal component ratio for modified fibrin hydrogels in order to provide favorable conditions for vascular development of endothelial and mesenchymal stem cell co-culture. It has been found out that the PEGylated fibrin hydrogels can support 3D cell growth in HUVECs and hASCs co-culture. The microporous filamentous hydrogel prepared from PEGylated 5 : 1 fibrinogen and using the 1 : 0.2 protein to thrombin ratio had the most favorable microenvironment for cell distribution, growth and development in the studied co-culture that resulted in high levels of expression of proteins required for angiogenesis.

The morphology and immunophenotype of female colostrum adherent cells with the help of CD3, CD31, CD34, CD45, CD68, vimentin, and osteocalcin antibodies panel was studied in short-term (6—7 days) culture in vitro. Approximately equal (1 : 1) ratio of fibroblast-like and rounded cells was observed in 20 % of cultural flasks. The cells with regular shape mixed with single fibroblasts were noted in 80 % of cultural flasks. The diameter of spreaded cells varied within 10—100 mm. All cells adhered to plastics did not express CD3 and interacted slightly (sl) with antibodies to CD31, CD34, and CD45. At the same time, adherent cells with intensive CD68, vimentin and osteocalcin staining have been revealed. Literature data allows to interpret CD68+CD3–CD31slCD34slCD45sl immunophenotype of significant part of mother colostrum adherent cells as belonging to monocyte-macrophage lineage. Marked expression of stromal antigens (vimentin, osteocalcin) in 40—45 % adherent cells in cultural medium without osteogenic supplements (beta-glycerophosphate, ascorbic acid, dexamethasone) proposes an existence of osteoblasts fraction differentiated in colostrum from mesenchymal stem cells under an action of breast milk humoral factors.

Development of local or general forms of prostate cancer (PC) depends on formation of metastasis the biological nature of which is based on epithelial mesenchymal transition (EMT). ÅÌÒ presents highly conservative reversible program that is maintained by specific transcription factors which suppress E-cadherin expression and support production of mesenchymal polarity factors. The goal of this work was to study the functionally distinct markers in malignant prostate tissue of patients with prostate cancer using the histological evaluation, reverse polymerase chain reaction and immunobloting. Our results showed that mostly evident alterations in prostate tissue of patients with prostate cancer were associated with the cells of basal layer. Expression levels of the markers of this layer: Å-cadherin and ÑK5, were decreased, while that of AMACR — increased. These results support an idea that the basal cells are primarily targeted during transformation and acquired the luminal phenotype in the course of the following differentiation. The functional analysis of these results may be performed in future using selected prostate cancer stem cells.

The human adipose-derived mesenchymal stem cells was shown to be hepatic differentiated under influence of inductor factors. The differentiation of MSCs was induced by fibroblast growth factor-4, hepatocyte growth factor, oncostatin M and dexamethasone. The influence of quercetin on the hepatic differentiation of MSCs in culture was investigated. The adding quercetin into induction medium (1 or 10 mmol/l) enhanced the manifestation of signs of hepatic differentiation MSCs such as urea secretion, cytokeratin 19 and a-fetoprotein synthesis. Quercetin modulating action on the CYP1A — cytochrome P450 activity in differentiated cells was found. MSCs which was differentiated in the presence of quercetin had a higher viability and resistance to oxidative stress.

A new human embryonic stem cell subline SC6-FF has been derived from SC6 cells in allogenic feeder-free culture system. Extracellular matrix proteins and conditioned medium from mesenchymal stem cell line SC6-MSC were the key components of the feeder-free culture system that therefore was allogenic for SC6-FF cells. SC6-FF subline has underwent more than 100 cell population doublings and retained normal diploid human karyotype: 46, XX. The average doubling time of the cell population was 23.7 ± 0.8 h that does not differ from that for the parent SC6 line. The presence of undifferentiated hESCs markers, alkaline phosphatase activity, Oct-4, SSEA-4 and TRA-1-60, has been verified by histochemical and immunofluorescence analysis. Non-directional differentiation of SC6-FF subline has led to development of cells that differ in size and morphology from the cells in the parent population. These cells demonstrate the ability of differentiation in the derivates of three germ layers by expressing the characteristic markers of the ectoderm (alpha-fetoprotein), mesoderm (a-actinin) and endoderm (a-fetoprotein) cells. We can conclude that the obtained characteristics of the new feeder-free SC6-FF sub-line correspond to the status of the human embryonic stem cells.

At the moment, the main location of the regional areas of neural stem cells in the adult brain is considered to be subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampal formation. However, the neural stem cells are not located chaotic in these areas, and they are localized in special niches — structural microenvironment that enables them to maintain identity, affect its proliferation and the fate of her descendants. The components of this microenvironment are intercellular interactions, the relationship with the blood vessels, extracellular matrix and specialized areas of basement membrane. The article describes of the neurogenic niches and the mechanisms controlling cell division and differentiation of progenitor cells.

Scanning electron microscopy and histologic analysis were used in the comparative in vivo study of resorption of chitosan fibers implanted into endomysium and perimysium of a rat latissimus dorsi muscle. It was demonstrated that the mechanism and rate of chitosan fiber resorption depend on the position of fibers in muscular tissue. After implantation of chitosan fibers into endomysium (when chitosan was in direct contact with muscle fibers), the formation of cross-sectional cracks, fragmentation of implanted fibers and its partial resorption were observed in 14 days. Complete chitosan resorption in endomysium occurred after 30 days only. Chitosan fibers implanted into perimysium preserved integrity for 7 days, and fibrous tissue was formed around implants. After 45 days of exposure, no signs of chitosan fiber destruction were registered in this case. Biocompatibility of chitosan fibers proved by effective adhesion and proliferation of mesenchymal stem cells on their surface.

Our recent findings clearly demonstrate that human endometrium-derived mesenchymal stem cells (hMESCs) respond to the sublethal oxidative stress by the premature senescence induction via ÀÒÌ/Chk2/p53/ p21/Rb pathway. Furthermore, based on the application of the SB203580 (SB) we suggested p38 MAP-kinase involvement in senescence progression. However, there are several disadvantages concerning this inhibitor: 1) using SB would not be suitable for in vivo experiments due to toxicity issue; 2) the poor kinase selectivity profile of SB complicates interpretation of the obtained data. Here, in order to confirm the implication of p38 in the H2O2-induced senescence of hMESCs, we applied another highly specific inhibitor of p38 — BIRB796 (BIRB). In presence of BIRB we revealed cell size decrease, reduction in the levels of reactive oxygen species, partial restoration of proliferation and increase in Rb phosphorylation levels in comparison to H2O2-treated hMESCs. Summarizing the obtained results we can postulate p38 implication in H2O2-induced senescence of hMESCs, and suggest p38 inhibition as a promising approach in prevention of premature senescence.

Resident stem cells of the heart are denoted as heterogeneous population of immature cells, which reside in the myocardium and characterized by their ability to self-renewal and are multipotent differentiation capacity into cardiomyocyte-like and vascular like cells. CSCs were originally isolated directly by long enzymatic digestion of heart tissue and selection using stem cell markers. However, long exposure to enzymatic digestion and small myocardial sample size can affect the possibility of obtaining a significant amount of viable cells. To avoid these problems, we developed a method consisting of growing of the CPC in explant culture and subsequent immunomagnetic selection.

A new approach to the description of the stem cells emergence in the development of multicellular organisms has been proposed based on a formalized description of the formation of elementary units of multicellularity — «gistions» by purchasing and implementing potentials for implementation of the procedure of division of functions between the cells. The system of gistions is shown in the form of the periodic table, which allows to predict the structure of the development and to measure it. The laws of conservation potentialities in gistions were suggested, explaining the origin of the stem cells. For the quantitative characteristics of development the experimentally determined parameters were described. Using it one can not only find a common pool of potentials, but also divide them into separate species and, thus, to talk about the structure of the pool and characterize changes in its development.

The reactions of the regional lymph nodes, caused by implantation of the autologous multipotent stromal cells of bone marrow origin (AMSCBMO) to accelerate the healing of mandibular bone defect were studied by fluorescent microscopy in inbred male Wag rats aged 6 months (n=62). After the introduction of polyhydroxyalkanoate transplant containing adsorbed AMSCBMO with a transfected Green Fluorescent Protein (GFP) gene into a damaged bone area, the lymphoid nodules in submandibular lymph nodes demonstrated the appearance of numerous large macrophages containing multiple oval fluorescent inclusions in the cytoplasm. The number of these macrophages increased within 2 weeks after surgery and then began to decline. Apparently, AMSCBMO introduced in this way, were partially absorbed by macrophages. After destruction of the structures formed from AMSCBMO, the debris was also phagocytized by macrophages. In either case, these macrophages appeared in the germinal centers of lymphoid nodules in lymph nodes, where the induction of immune responses against DNA and GFP protein was probable.

Recently, more and more attracted the attention of cell therapy, which requires a study of the efficacy and safety of allogeneic MSCs transplantation in acute and chronic inflammatory reactions. The aim of our study was to examine the effectiveness of transplantation of allogeneic mesenchymal bone marrow stromal cells for the healing of surgical wounds the glandular stomach in rats.

Multipotent mesenchymal stromal cells (MMSCs) are essential for regeneration and tissue homeostasis. The investigation was focused on the functional state of MMSCs isolated from human adipose tissue and exposed to simulated microgravity in vitro by RPM (random position machine). The results point to an increase of proliferative potential, decrease of the lisosomal compartment activity, and reductions in cell size and granularity. Evaluation of the paracrine activity in relatively static control revealed increased IL-8 production and decreased IL-6 production. *Our .data supplement previous findings and allow conclude about universality of the mesenchymal cell reaction to simulated microgravity. The investigation did not detect signs of cell stress in this environment.