The ex vivo maintenance and expansion of hematopoietic stem cells and early progenitors is necessary for the successful treatment of hematopoietic and immune diseases. Multiple attempts to improve the expansion of hematopoietic stem cells (HSCs) by their cultivation in the presence of growth factor cocktails have so far failed. Novel approaches aimed at conserving the earliest precursors in their undifferentiated state are needed. These approaches should take into account local regulatory factors that are present in the HSC microenvironment and the three-dimensional architecture of their niche. In the present study, we compared the effects of two Notch ligands, i.e., Jagged1 and DLL1, on murine and human hematopoiesis in vitro. Our observations indicate that the stromal expression of Notch ligands increases the production of both the total and phenotypically early murine and human hematopoietic cells in the co-culture. On one hand, this study demonstrates the similarity of effects of stromal expression of Notch ligands on murine and human hematopoiesis in vitro. On the other hand, our study revealed a number of cell type and ligand-specific variations that are systematically described below. It seems that the effects of SCF cytokine addition on murine hematopoiesis in vitro depend on the stromal context and are oppositely directed for Jagged1 and DLL1.

Recently, a number of new highly efficient antibody-based anticancer therapeutics have emerged. These receptor-binding antibodies have beneficial toxicity profiles associated with relatively mild side effects. Therefore, the search for novel surface proteins that are present on cancer cells and play important metabolic or defensive roles has intensified. Additionally, the therapeutic stimulation of patient's immune system in order to aim its components, specifically, phagocytes and cytotoxic T-lymphocytes, at tumor cells is gaining traction. This review is focused on the CD47 surface receptor, a ubiquitously expressed molecule, which could nevertheless serve as a therapeutic target due to its ability to simultaneously stimulate both natural and adaptive immune response.

Biological limitations related to the brain regeneration and stem cells transplantation as well as the factors influencing the brain plasticity following the brain injury, including epigenetic regulatory mechanisms, are presented. Non-invasive transcranial microelectrostimulation is considered as a perspective method of polysystemic influence on endogenic mechanisms of brain recovery.

To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program.

To analyze clinical and laboratory data and treatment results in patients with light-chain deposition disease (LCDD).

Endometrial mesenchymal stromal cells (eMSCs), along with mesenchymal stromal cells (MSCs) isolated from other tissues, are promising for use in regenerative medicine. The benefits of eMSCs include their presence in adults, simplicity of isolation, high proliferative and differentiation capacity. In this study, we have employed the flow cytometry technique to assess expression of 28 molecular markers on the surface of two eMSCs cultures. The culture of MSCs isolated from Wharton's jelly of the umbilical cord (uMSCs) was used as a reference, because uMSCs were studied in details earlier and demonstrated their effectiveness in vivo. Both types of MSCs demonstrated similar expression profiles. They included stem cells surface molecules, cell adhesion molecules and their ligands, some receptor molecules responsible for cell metabolism and proliferation, as well as immunological response molecules.

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.

The review represents a modern concept about cells-molecular basis of mechanisms of neuro-immune interactions, the data on the effects of destabilizing factors (electric pain stimulation, rotation, cold and psychoemotional stress) on the functioning of neurons and immune cells. It must be underlined, that under the stress conditions take place the alterations of ligand-receptors interactions on the membrane of lymphocyte. In particular the reaction of these cells to regulating signal - application of Interleikin-1 grow up after mild stress, but it falls down after an influence of severe stress factors. Special attention is paid to the role of the orexinergic system in mechanism of realization of CNS reactions to application of antigens. In the present work the possible methods of correction of imbalance in functional interactions between nervous and immune systems, caused by different destabilizing factors, are reviewed.

The article presents characteristics of morphogenesis of stem hematopoietic cells at early stages of development. At the same time, analogy is marked concerning morphogenesis of hematopoietic cells in differentiating period of mesenchyme and terminal period of development of bone marrow cells. The role of stem mesenchyme cells in development of hematopoietic cells and elements of their micro-environment is observed.

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.

This article describes the results of systemic transplantations of cardiomyoblasts grown from autologous or allogeneic bone marrow-derived mesenchymal stem cells, in the complex therapy of the late radiation da- mage of the heart, which developed after radiation therapy in 16 female patients with Hodgkin disease (HD) or breast cancer (BC). The cell therapy drastically improved the efficacy of the drug treatment, which earlier was the only option for the therapy of the radiation damage of vital organs. The effect of such therapy was clinically observed in the patients already in the first year of observation, and consisted in the decrease of the degree of the cardiac failure severity and improvement of their quality of life in the absence of HD or BC progression.

The genotypic features of morphogenesis and regeneration in vitro for five maize inbreds of perspective breeding Lancaster heterotic group compared to representatives of others heterotic groups – PLS61, A188 and Chi31 were studied. It was identified that the ratio of such types of morphogenesis as organogenesis and embryoidogenesis in callus culture was determined by the explant genotype and the concentration of sucrose in the medium for callusogenesis. The frequency of embryoidogenesis as the most effective type of morphogenesis for further regeneration in Lancaster inbreds averaged about 40.0 ± 12.8 %, while for other heterotic groups it was only 14.0 ± 4.0 %. For Lancaster heterotic group sucrose at the concentration of 30 g/l in the medium for callusogenesis provided further regeneration through embryoidogenesis at the level of 26.5 ± 15.4 %, but sucrose at the concentration of 60 g/l provided it at 57.7 ± 19.8 %. For inbreds which represent other heterotic groups sucrose content in the medium for callusogenesis did not affect further regenaration, the level of embryoidogenesis at 30 and 60 g/l sucrose amounted 11.0 ± 7.0 and 15.0 ± 4.8 % correspondingly.

The effectiveness of two transplantation methods of human hepatocellular carcinoma cells HepG2 and allogeneic mesenchymal stromal cells of adipose tissue (AT MSCs) into mice was compared in order to select the most effective for liver damage repair. Considerable advantage of cell transplantation into the spleen compared with intraperitoneal administration was shown. It is found that, under similar conditions of transplantation, AT MSCs are detected in liver tissue in smaller quantities than human hepatocellular carcinoma cells HepG2; differences in cell localization of these types of cells in the liver are revealed. A tendency to decrease in the degree of fibrotic changes in liver tissue after transplantation of AT MSCs and to a greater extent after transplantation of AT MSCs, pretreated with interleukin-6, was traced.

Nuclear lamins form nuclear lamina localized under the inner nuclear membrane. It was previously considered that the nuclear lamina predominantly plays a structural role, however, its involvement have been recently described in the regulatory processes such as chromatin organization and gene transcription. It is known that mutations in the LMNA gene lead to the development of a large number of diseases, laminopathies, which mainly affect mesenchymal tissue. Nowadays, the mechanisms by which the lamina can regulate cell differentiation remain incompletely understood. In the present work, we have studied the effect of LMNA gene mutations on the process of muscle differentiation of primary satellite cells and Ñ2Ñ12 cell line. The genome of satellite cells and Ñ2Ñ12 cell line was modified by the introduction of lentiviral constructs encoding LMNA G232E associated with the development of muscular dystrophy Emery—Dreyfus and LMNA R571S associated with the development of dilated cardiomyopathy. The morphology of the cells was estimated using immunofluorescence, the expression level of myogenic genes were analyzed by qPCR. We have shown that the analyzed mutations reduce the ability of cells to differentiate, to fuse and to form myotubes. We have suggested that it is due to enhanced expression of markers at the early stages and to reduced expression markers at the late stages of myogenesis. Therefore, mutations in nuclear lamins can influence the process of muscle differentiation.

Cultivation of cells under artificial conditions is one of the necessary procedures when working with stem cells. At this stage, the cells lose control by the macroorganism, becoming independent systems. Therefore, during the passaging of the cells, the probability of undesirable modifications is increased. At present, there is not enough data on the first indications about modification of the cultured cells and when they can appear. In the work, the rabbit medullary mesenchymal stromal cells (MSCs) were studied during 5 passages after producing primary culture. The area and the spreading coefficient of a cell were used to evaluate the cell state. The measurements were made 1 h and 1 day after cell reseeding by analyzing digital images of intact living cells. During this time interval, the absolute values of the cell area increased with the passage number, whereas the increment of the cell growth area did not depend on the passage number. It is possible to distinguish three groups of cells. Smaller cells (the 1st group) prevail in cell population of the 1st passage. Next, their proportion is decreased and the proportion of larger cells is increased. Passaging of the cells does not influence their spreading coefficient.

The nucleus of mouse two-cell embryos houses the coilin-containing bodies of two types: 1) 1—3 large spherical structures of 1 mm and 2) small foci, which vary in number in different blastomeres. The largest coilin-containing structures, unlike the smallest ones, contain RNA polymerase I, nucleic acid chaperon YB-1, and also actin. Neither large nor small coilin-positive domains contain symplekin, one of the signature components of histone locus bodies. In the nuclei of late two-cell embryos, symplekin localizes to 1—2 well-formed roundish bodies that are observed both in close proximity to the coilin-positive structures and far away from them. Large coilin-containing bodies were not observed in embryos at the morula stage as well as in the nuclei of late two-cell embryos after artificial suppression of transcription activity. Thus, a population of coilin-containing bodies in the nuclei of late two-cell embryos of mice is heterogeneous in morphology and molecular composition. It could be assumed that the largest coilin-containing bodies are provisional nuclear domains that are formed at the background of significant changes of nuclear metabolism at the final stages of embryonic genome activation and the initial stages of reactivation of nucleolar transcription.

Elaboration of new methods of correction of microcirculatory disorder in the brain caused by persistent high blood pressure is a topical task both for medicine and for biology. We studied influence of intracerebral transplantation of human mesenchymal stem cells (MSCh) to cerebral microcirculation in young (4 months) and aged (12 months) spontaneously hypertensive rats (SHR). It was shown that transplantation MSCh promoted the rise of the density of microvascular network of young SHR ca. 1.6-fold; density of the arteriolar area of microvascular network of the pia mater increased ca. 1.9-fold. The density of microvascular network of aged SHR increased ca. 1.4—1.5-fold after transplantation MSCh. The perfusion and tissue saturation of sensorimotor cortex of young SHR increased to the level of young normotensive rats, and in aged SHR the perfusion and tissue saturation of sensorimotor cortex was not increased. Conclusion: the intracerebral transplantation MSCh almost completely leveled the pathological changes of the microcirculation in the sensorimotor cortex of the brain of young SHR and improved unimportantly microcirculation in aged SHR.

Mesenchymal stem cells (MSCs) are present in almost all organs and tissues of the organism. It is believed, that MSCs could be transformed into cancer stem cells spontaneously or under influence of genotoxic factors and trigger the growth of tumors. The aim of this work was to study the possibility of malignant transformation of cultured MSCs from murine bone marrow (MSCs-BM) after g-irradiation in vitro and characterize of biochemical and histological features of the tumors that developed after transplantation of MSCs-BM into syngeneic mice. Tumors were observed in 3—4 months after MSCs-BM transplantation. After administration of MSCs-BM irradiated at a dose of 1 Gy, tumors were seen in 2 of 5 mice. After transplantation of MSCs-BM irradiated at a dose of 6 Gy, tumors were found in all 5 of 5 mice. In the case of control MSCs-BM, only one tumor appeared in 6 months after transplantation. The telomerase activity was two times higher in the tumor developed from 6 Gy irradiated MSCs-BM than from 1 Gy irradiated MSCs-BM. The tumors developed from control and irradiated MSCs-BM were classified as multicomponent mesenchymomas («mixture of sarcomas»). Histological examination showed that tumors contained tissue areas of different histogenesis. Thus, MSCs-BM g-irradiated at doses of 1 and 6 Gy and, much less frequently, control MSCs-BM can transform into tumor cells and induce development of multicomponent mesenchymomas.

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.