Despite the widespread use of intestinal cystoplasty, urinary bladder substitution remains a challenging problem due to the complexity of operations and the potentially high risk of complications. A promising alternative may be bio-engineered collagen-based matrices containing stem cells or their secretions.

Stem and progenitor cells being introduced into the body have the ability to stimulate regeneration of tissues and organs by differentiating into specialized cells. Stem cell therapy is used in urology to treat various disorders, including erectile dysfunction, urinary incontinence, Peyronies disease, and male infertility. This review presents the results of international preclinical and clinical research on stem cell based medications for treating the above diseases. The most promising appears to be the use of adipose tissue-derived mesenchymal stem cells.

Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to identify individuals with an increased risk of TGCTs.

The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells. However, to improve the effectiveness of such treatment it is necessary to search for more optimal sources of progenitor cells, as well as to evaluate the possibility of using descendants of these cells differentiated in vitro. In this study we isolated stromal cells from the liver biopsies of three patients with alcoholic cirrhosis, conducted their morphological and phenotypic analysis, and evaluated the hepatic potential of these cells in vitro. The stromal cells isolated from fetal liver were used for comparison. The results of this can serve as a basis for the development of a new method for the treatment of end-stage liver disease. The stromal cells isolated from the liver biopsies for a long time proliferate in a culture and this which makes it possible to expand them to large amounts for subsequent differentiation into hepatocyte-like cells and autologous transplantation.

An experimental model of lower limb ischaemia induced by ligation of the femoral artery in CBA-line mail rats was used to study efficacy and effect of intramuscular administration of autologous bone-marrow stem/progenitor cells on the process of angiogenesis. Based on the findings of laser Doppler flowmetry it was shown that administration of autologous stem/progenitor cells promotes acceleration of the processes of neoangiogenesis, which was confirmed by the results of histological study.

The authors share their experience in comprehensive conservative treatment of patients presenting with chronic lower limb ischaemia (CLLI) associated with atherosclerosis of peripheral arteries by means of the first Russian registered gene therapeutic agent "Neovasculgen" (plasmid with the vegf165 gene), analysing the long-term outcomes of treating a total of 45 patients with stage II and III CLLI according to the classification of Pokrovsky-Fontain. The patients were followed up for 5 years. Efficacy of treatment was assessed by registering the dynamics of the pain-free walking distance (PFWD), linear blood velocity (LBV), ankle-brachial index (ABI), as well as the limb salvage rate and survival of patients. All patients showed good tolerance of treatment, with neither side effects nor complications noted. Clinical improvement in stage IIB CLLI was observed in 91% of patients with complete stabilization of the clinical course during 5 years. The limb salvage rate in this group amounted to 95%, with the survival rate equalling 82%. In patients with stage III CLLI, improvement was noted in 78% of cases, manifesting itself by a decrease of its degree to stage IIB (44.4%) and to stage IIA (33.3%). Progression of CLLI followed by amputation was registered in 22% of cases, with the survival rate of 78%. Hence, the use of a single course of combined treatment including the gene therapeutic agent "Neovasculgen" in patients with stage II and III CLLI resulted in a persistent positive effect in a considerable majority of patients in the remote period of not less than 5 years.

The Piwi protein and its orthologs are considered as the key components of the piRNA machinery implicated in transcriptional silencing of transposons. Неre, we show that nuclear localization of the Piwi protein is required not only for transposon repression, but also for proper differentiation of germline stem cells (GSCs). piwi^(Nt) mutation that causes loss of nuclear Piwi and its retention in the cytoplasm leads to the accumulation of undifferentiated GSC-like cells. The analysis of piwi^(Nt) mutation in combination with a bam gene mutation blocking GSC differentiation shows that the loss of nuclear Piwi decreases GSC proliferation rate. This is accompanied by the accumulation of DNA double-strand breaks in GSCs that may be caused by transposition events. Here, for the first time a set of transposons repressed by Piwi in GSCs and surrounding niche cells has been identified. The present study together with our previous data show that nuclear and cytoplasmic Piwi can regulate different stages of the functioning of germinal cells: cytoplasmic Piwi is sufficient to maintain GSCs, while nuclear Piwi localization is necessary for their proper proliferation and differentiation.

Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-κB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism.

The quantitative regularities of changes of cancer stem cell (CSC) population were explored after local γ-irradiation of experimental tumors (murine melanoma line B16). CSCs were detected by the ability of these cells to exclude Hoechst 33342 fluorescent dye and to form a so-called side population (SP) under flow cytometry study. In the control group of unexposed mice a positive correlation was found between the proportion of CSCs (SP) and tumorweight at the initial stage of growth (R = 0.77, p = 0.009). In the advanced stages of tumor growth similar relationship was not revealed. Statistically significant increase in the proportion of CSCs (SP) occurred 2-5 days after exposure of tumor to a dose of 10 Gy as compared to control; this index returned to the control level 8 days after irradiation. On the second day after exposure to radiation a linear correlation between the percentage of CSCs and a radiation dose in the range of 2-10 Gy was established (R = 0.98, p = 0.003), confirming a higher radioresistance of this population as compared to other cells not only in vitro (as it was previously shown by us and other authors), but also in vivo. These results suggest the possibility of application of this model system to assess the CSC sensitivity to various antitumor agents in vivo, including preclinical trials, and clarify the details of the practical application of this method.

The anabolic effects require brief exposures to higher than average PTH concentrations. The catabolic effects result from pathological conditions in which parathyroid glands secrete too much hormone continuously at a sustained level. The aim of the present study was observance of intermittent (I-PTH) and continuous (C-PTH) PTH 1-34 administration influence on bovine chondrogenic progenitor cells (CPC) differentiation. Alcian blue was used to determine proteoglycan accumulation in CPC monolayer cultures. Thus in plates containing CPCs in C-PTH media chondrogenic differentiation was indicated by intensive proteoglycan accumulation in extracellular matrix. CPCs monolayer cultured in osteogenic media were subjected to Alizarin Red staining for matrix mineralization detection. Intense staining was revealed in I-PTH cells in comparison with C-PTH plates. The data obtained by monolayer cultures histological staining were confirmed by PCR analysis.

Effective treatment of malignant brain tumors is still an open problem. Location of tumor in vital areas of the brain significantly limits capasities of surgical treatment. The presence of tumor stem cells resistant to radiation and anticancer drugs in brain tumor complicates use of chemoradiotherapy and causes a high rate of disease recurrence. A technological improvement in bioselection and production of recombinant resulted in creation of viruses with potent oncolytic properties against glial tumors. Recent studies, including clinical trials, showed, that majority of oncolytic viruses are safe. Despite the impressive results of the viral therapy in some patients, the treatment of other patients is not effective; therefore, further improvement of the methods of oncolytic virotherapy is necessary. High genetic heterogeneity of glial tumor cells even within a single tumor determines differences in individual sensitivity of tumor cells to oncolytic viruses. This review analyses the most successful oncolytic virus strains, including those which had reached clinical trials, and discusses the prospects for new approaches to virotherapy of gliomas.

Multipotent mesenchymal stromal cells (MSC) are now considered to be a perspective multifunctional treatment option for radiation side effects. At present.a great number of sufficient evidence has been collected in favor of therapeutic effects of MSCs in acute radiation reactions. It has been shown that MSC-based products injected locally or systemically have therapeutic effects on irradiated organs and tissues. This review presents summarized experimental and clinical data about protective and regenerative effects of MSCs on different radiation-injured organs and tissues; the main probable therapeutic mechanisms of their action are also discussed.

To evaluate the damaging effects of cisplatin on MMSCs from adipose tissue in a phase of active proliferation and the state of the monolayer, this was exposed at standard (20%) and reduced to 1% and 5% level of oxygen.

Biopsy specimens of the thymus were studied in children aged under 11 months (n = 77) with congenital heart defects and circulatory hypoxia of varying severity. Histological sections were stained with hematoxylin-eosin and Shubich's method (to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed by immunohistochemistry. The ultrastructure of thymic tissues was also examined. It was found that the severity of hypoxia determined the morphological changes in the organ associated with a development of large complex of tissue reactions. A disruption of internal structure and a loss of integrity of epithelio-reticular cells and thymocytes were demonstrated in ultrathin sections. Thymocyte proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in all the zones of the thymus. The degree of hypoxia affected the redistribution of CD3+ lymphocytes leading to their accumulation in the medulla. The processes of endogenous regeneration took place which involved the cells of fibroblastic line and progenitor cells (CD34+) together with active formation of new blood vessels. These findings suggest that the morphological changes identified in the tissues of the thymus are a manifestation of tissue adaptation to hypoxia of varying severity under conditions of endogenous regeneration, simultaneously reflecting the processes of substitution cytogenesis.

Currently there is no data on peripheral arterial disease prevalence in Russia.

This systematic review aims to analyze molecular markers of cancer stem cells. Only studies that confirmed tumor-initiating capacity of this population by in vivo assay in immunodeficient mice were included. Final sample of papers that fully correspond with initial aim consists of 97 original studies. The results of their analysis reveal that markers commonly used for cancer stem cells deriving were as follows: CD133, СD44, ALDH, CD34, CD24 and EpCAM. The review also contains description of molecular features of some cancer stem cell markers, modern approaches to cancer treatment by targeting this population and brief assessment of cancer stem cell theory development.

In the previous cytogenetic study of new human stem cell line 4BL at the 205th passage we observed the ploidy of chromosomal set and regular aberrations. To investigate the nature of monosomy of certain chromosomes the array CGH and FISH analyses have been used. The aberrations of chromosomes have been identified in all the cases of monosomies previously revealed by G-banding. The largest changes of the DNA balance have been detected in the chromosomes 2, 4, 10, 13 and 17. The probable cause of the monosomies of chromosomes 4, 10, 13 and 17 is massive loss of the genetic material. The monosomy of the second chromosome pair is caused by significant transformation one of the homologs in a type of numerous duplications and formation of der(2)t(2;?)(q21;?). Due to application of array CGH the regions of the structural aberrations of the chromosomes 2, 4, 10, 13 and 17 have been concretized, what permitted to perform their clarifying identification by multicolored FISH method. The results obtained by us confirm the hypothesis about coordinated appearance of the deletions and duplications and their stabilization impact on the transformed chromosomes.

3-Hydroxy-3-methylglutaryl-CoA reductase (HMG1) catalyzes the formation of mevalonic acid, the key intermediate of the cytosolic isoprenoid synthesis pathway. The parameters of stem and leaf growth were studied in the transgenic tobacco plants that express the HMG1 gene in both sense and antisense orientations towards the constitutive promoter. The transgenic plant height did not significantly differ from that of the control plants, though the plants carrying the sense copy of the HMG1 gene were considerably taller than plants that carried the antisense gene copy. Plants carrying an extra copy of the HMG1 gene were also characterized by increased leaf area. The number of mesophyll cells calculated per square unit of transgenic plants leaves was smaller than in the control plant leaves, though their volume was not considerably changed in any of the variants, suggesting changes in the cell packing density in leaves.

Transgenic clones of mouse embryonic stem cells of the RI line were -received by transfection of plasmid linear vectors. The changes in the transgene structure during its integration into the genome of the target cells were investigated. Displacements were found on the flanks of the integrated transgene. It was found that multicopy tandem structures are formed in head- -tail orientation at the transgene integration. It was noted that the number of copies of the integrated transgenes varies considerably, but the introduction of DNA fragments from the nuclear shells into the flanks of the transgene normalizes the number of its copies.

The complexity of the pathogenesis and insufficient knowledge about the slow retroviral infections, which include equine infectious anemia, necessitates finding an adequate laboratory model for the study of the infection process and immunogenesis to create means of prevention and treatment of diseases. Data about strains and cellular tropism of the virus are discussed. It was shown that mouse embryonic stem cells (ESCS) exhibited unique properties and characteristics. In contrast to fibroblasts and other cell types, these cells can be considered as a new cell system for studying EIAV in vitro and in vivo. Under differentiation-inducing conditions they are able to reproduce in vitro embryogenesis cells and form cells of three germ layers. Differentiation of mouse ESCs in the direction of hematopoiesis could contribute new knowledge and understanding of viral tropism EIAV in vitro. ESC can be returned back to the early pre-implantation embryo. Once in the germ cell environment, they participate in the formation of tissues and organs of the developing fetus. Thus, the adaptation of the mouse ESC to the equine EIAV through genetic transformation makes it possible to get closer to the creation of a laboratory model for the study of the in vivo immune response in the lentiviral infection.