The aim of this research was to study the migration of multipotent mesenchymal stromal cells (MMSC) in old laboratory animals under physiological conditions and after liver resection. Different routes of administration were used: to the caudal vein, intraperitoneal, hepatic artery, portal vein. Studies have shown the ability of the old organism to respond to changes in the directed migration of MMSCs in the tissues that have undergone the greatest damage, which may be due to the production of connective tissue of the damaged organ chemoattractant. In contrast intraperitoneal, other delivery methods MMSC: tail vein, v. portae, a. hepatica, are more effective.

The followings were estimated in the 3-5 and 15-17 months 129/Sv cuprizone- and melatonin-treated mice: the number of activated T-lymphocytes, macrophages, neural stem cells (determined by CD3+, Mac1+ and nestin+ markers), the structurally unchanged neurons, the malondialdehyde (MDA) content and the antioxidant enzyme activities in the brain; the blood thymus hormone thymulin level; and the behavioural indices. The mice were fed with cuprizone for 3 weeks. From the 8th day of the cuprizone treatment the mice were injected with melatonin (1 mg/kg, at 18:00 daily). As a result, the number of the CD3+-, Mac1+-, and nestin+-cells and the MDA content increased while the glutathione peroxidise (GP) activity decreased in the brain of young and aged mice under the influence of cuprizone. In mice of both age groups the proportion of unchanged neurons in the central nervous system, motor and emotional activity and muscle tone were decreased. Regardless of the age of the mice the injections of melatonin decrease the number of СD3+, Мас1+-cells, content of MDA, increase activity of GP and thymulin level. Decrease of the number of nestin+-cells coincides with the growth of the number of unchanged neurons. The effect of both neurotoxin and melatonin on immune factors, the structure and functional state of neurons was more pronounced in young mice. Thus, the positive effect of melatonin in young and aged mice with the cuprizone-induced demyelination was realized mainly through the pathogenetic factors of pathology.

Ischemic cardiomyopathy is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ischemic cardiomyopathy. Several stem cell types, including cardiac-derived stem cells, bone marrow-derived stem cells, mesenchymal stem cells, skeletal myoblasts, CD34+ and CD133+ stem cells have been used in clinical trials. Clinical effects mostly depend on transdifferentiation and paracrine factors. One important issue is that a low survival and residential rate of transferred stem cells blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ischemic cardiomyopathy mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical conditions, the particular microenvironment onto which the cells are delivered, and clinical conditions remain to be addressed. Here we provide an overview of modern methods of stem cell delivery, types of stem cells and discuss the current state of their therapeutic potential.

Secretion of 21 cytokines, chemokines and growth factors (LIF, SCF, SDF-1a, SCGF-b, M-CSF, MCP-3, MIF, MIG, TRAIL, GRO-a; IL-1a, IL-2ra, IL-3, IL-12(p40), IL-16, IL-18, HGF, TNF-b, b-NGF, IFN-a2, CTACK) has been studied in vitro in the culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in conditions of its osteogenic differentiation caused by 14-day contact with calcium phosphate (CP) surface with different roughness. Bilateral X-ray amorphous CP coatings were prepared on the samples of commercially pure titanium in the anodal regime using a micro-arc method. An aqueous solution prepared from 20 wt% phosphoric acid, 6 wt% dissolved hydrohyapatite nanopowder (particle diameter 10-30 nm with single agglomerates up to 100 nm), and 9 wt% dissolved calcium carbonate was used to obtain CP coating. hAMMSCs isolated from lipoaspirate were co-cultured after 4 passages with the CP-coated samples at final concentration of 1.5´105 viable karyocytes per 1.5 mL of standard nutrition medium (without osteogenic stimulators) for 14 days (a determination of [CD45,34,14,20], CD73, CD90 и CD105 cell immunophenotype; an analysis of secretory activity) and 21 days (alizarin red S staining of culture) with medium replacement every 3-4 days. Under conditions of in vitro contact with rough CP coating hAMMSCs differentiated into osteoblasts synthesizing the mineralized bone matrix; this was accompanied by 2-3-fold increasing ratio of [CD45,34,14,20]+ hemopoietic cells. The following humoral factors of hemopoietic niches acted as the signal molecules escalating in vitro the hemopoietic base in 14 days of differentiating three-dimensional culture of hAMMSCs: either leukemia inhibitory factor (LIF) and stem cell factor (SCF) cytokines under mean index of CP roughness Ra=2.4-2.6 mm or stromal derived factor-1 (SDF-1a, CXCL12 chemokine) under Ra=3.1-4.4 mm.

The basis of Central Research Institute of Dentistry and Maxillofacial Surgery in the period from 2015 to 2018 years there were 30 patients with primary hemiatrophy (group 1) and patients with hemiatrophy after reconstructive operations (group 2) who were examined and treated. The elimination of deformation of soft tissues was performed by combination of micro-, nano- and classical lipofilling in two sessions with an interval of 6 months. To determine the deficit of tissue volume on the affected side before and at the treatment stages, a computer tomography was performed with the construction of the mathematical surface of the face. A study of the nature of the changes in the underlying structures in each group was carried out using ultrasound scanning and LDF studies. The use of non-invasive research methods allows us to track the dynamics of skin transformation. Based on the results of the treatment in 2 groups, a combination of micro-, nano- and classical lipofilling did not only increase the volume and eliminate deformation soft tissue, but also transform the quality of the skin. Thus, the combination of various lipofilling methods allowed to achieve a more stable result and increase the efficiency of treatment.

To comprehensively assess the functional molecular biological status of different tumor cell populations in glioblastoma samples.

Homeodomain transcription factors play a significant role in adipocyte differentiation. The role of Pbx1 and Prep1, proteins of the TALE family (the three amino acid loop extension), was previously established in adipocyte differentiation of mesenchymal stromal cells and 3T3-L1 cell line. In this study, with the use of RNA interference technology we show that another transcription factor from the same family, Meis1, which is a core protein of mature cardiomyocytes, represses adipogenesis to a greater degree than its paralog Meis2. A number of Meis target genes, markers of adipocytes, are identified. This may indicate the transcriptional mechanism of the effect of Meis1 on the adipocyte differentiation of mouse preadipocytes.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for hematopoietic malignancies. The graft-derived donor lymphocytes are capable of eliminating the residual recipient malignant cells in the course of allogeneic immune response, thus decreasing the chances of a relapse of the disease. Foreign peptides of the recipient presented by the MHC molecules are able to elicit the immune response immunologically. These polymorphic peptides are known as minor histocompatibility antigens (MiHAs). MiHAs occur due to the nonsynonymous single nucleotide polymorphisms in human genome. Transfusion of T cells specific to MiHAs presented predominantly in the cells of hematopoietic origin will allow the targeted elimination of residual malignant clones avoiding undesirable damage to healthy tissues. To induce the immune response, the donor must be homozygous by the MiHA allele and the recipient must either be homozygous or heterozygous by the alternative MiHA allele. The therapeutic mismatch occurs in 25% of cases under the optimal frequency of allelic variants. Minor antigen ACC-1Y originates from polymorphism in the BCL-2A1 gene; its immunogenic mismatch occurrence approaches the theoretical maximum. In addition, BCL2A1 is overexpressed in cells of various lymphomas. ACC-1Y is presented on allele HLA-A*24:02, which is relatively frequent in the Russian population. Combination of these factors makes the minor antigen ACC-1Y a promising target for immunotherapy. Transfusion of donor CD8^(+) lymphocytes modified with transgenic MiHA-specific TCR is one of the promising methods of posttransplant leukemia therapy and relapse prophylaxis. We obtained a sequence of high-affinity ACC-1Y-specific TCR after the antigen-specific expansion of T cells derived from a healthy ACC-IY^(-/-) donor. We cloned this sequence into the lentiviral vector and obtained the assembled viral particles. Further, we transduced the CD8^(+) lymphocyte culture and demonstrated its antigen-specific cytotoxic activity. It is suggested that CD8^(+) lymphocytes modified by the described method could be potentially transferred to recipients as a therapy against relapse after allo-HSCT.

N^(6)-methyladenosine (m^(6)A) has been identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, and plays important biological roles in the regulation of cellular metabolic processes. However, its role in myogenic differentiation is unclear. Here, we altered the m^(6)A RNA methylation level by overexpression of METTL3, and explored the effect of m^(6)A RNA methylation on myogenic differentiation of murine myoblasts in vitro. The m6A RNA methylation level is regulated by exogenous methylation inhibitor cycloleucine (Cyc) and methyl donor betaine (Bet). Therefore, chemical reagents of Cyc and Bet were used to test the regulatory effect of m^(6)A RNA methylation on myogenic differentiation. Results showed that METTL3 and Bet positively regulated the m^(6)A RNA methylation levels, and Cyc negatively regulated m^(6)A RNA methylation levels. In addition, m^(6)A methylation positively regulated myogenic differentiation in murine myoblasts. These findings provide insight in the mechanisms underlying the effect of m^(6)A RNA methylation on myogenesis.

The fundamental question about the origin of cancer stem cells of urothelial carcinomas with luminal remains open. So far, no convincing evidence has been found to determine whether these events occur in a single cell, presumably basal, or are realized in different precursor cells of the urothelium. The potential of a number of potential stem markers as cancer stem cells in urothelial carcinomas and their prognostic significance are currently being investigated.

Today, transplantation of stem / progenitor cells is a promising approach for the treatment of heart diseases. The therapeutic potential of transplanted cells directly depends on the method of delivery to the myocardium, which determines their regenerative properties. It is important for the development of effective methods of cell therapy. In this paper, we performed a comparative study of efficacy of cardiac progenitor cell (CPC) transplantation by intramyocardial needle injections and by tissue engineering constructs (TEC) - "cell sheets" consisting of cells and their extracellular matrix. It has been shown, that transplantation of TEC in comparison with the intramyocardial delivery provides more extensive distribution and retains more proliferating cellular elements in the damaged myocardium, attenuates the negative cardiac remodeling of the left ventricle and promotes its vascularization.

Conducted high-resolution HLA-typing loci HLA-A, -B, -C, -DRB1 and -DQB1 by massively parallel sequencing of 150 potential donors of hematopoietic stem cells from the Republic of Kalmykia. In the studied population, four new alleles identified that not previously registered by the International Committee on the Nomenclature of Factors of the HLA-system of WHO. During the HLA-typing identified: 29 alleles at the HLA-A locus, 44 - at the HLA-B locus, 26 - at the HLA-C locus, 15 - at the DQB1 locus, 37 - at the HLA-DRB1 locus. The following alleles have a frequency of more than 10%: HLA-A*02:01 (11,7%), HLA-A*01:01 (11%), HLA-B*51:01 (10,3%), HLA-B*58:01 (10,3%), HLA-C*06:02 (17,7%), HLA-C*03:04 (10,3%), HLA-C*03:02 (10%), HLA-DQB1*03:01 (26,7%), HLA-DQB1*02:02 (10%), HLA-DRB1*07:01 (11,7%). The most common HLA-A-B-C-DQB1-DRB1 haplotype is A*02:05-B*50:01-C*06:02-DQB1*02:02-DRB1*07:01 (3,7%). Deviations from the Hardy - Weinberg equilibrium not identified.

We have established earlier that 835-nm infrared laser irradiation results in a dose-dependent growth inhibition of human mesenchymal stem and melanoma cells and is able to induce cell death. In this work we have demonstrated that hydrogen sulfide donor NaHS is able to protect both cell types from the negative action of laser irradiation and the magnitude of protection depends on NaHS concentration. The mechanism of cell protection by NaHS is primarily attributable to its effects on intracellular processes occurring after irradiation, since the protective effect does not depend on whether NaHS is added before or after irradiation. Moreover, NaHS is able to exert its protective effect even when added 6 hours post irradiation.

The neural crest (NC) in embryos of vertebrates represents a cell population formed at the border of the neural plate. These cells retain pluripotency, express a set of specific markers, and become multipotent upon their migration away from the neural tube to give rise to numerous derivatives. The genes specific for vertebrate NC appeared in evolution long before vertebrates. Abnormal development of NC cells causes numerous pathologies in humans.

Vascular grafts made of polytetrafluoroethylene and polyethylene terephthalate have widely been used in cardiovascular surgery. The causes of delayed colonization of such grafts by endotheliocytes and mesenchymal stem cells have not been adequately investigated. The authors examined the effect of polyethylene terephthalate on the functional activity of human bone marrow mesenchymal stem cells and endothelial progenitor cells in vitro. Proliferation (MTT assay, real-time cellular impedance), migration (Boyden chamber, real-time cellular impedance), and nitric oxide production (spectrophotometciacally) by progenitor endothelial cells and mesenchymal stem cells were assessed with and without the presence of polyethylene terephthalate. The functional activity of the cells was shown to depend on the presence of polyethylene terephthalate in a well with cells. Thus, polyethylene terephthalate turned out to exhibit a toxic effect on progenitor endothelial and mesenchymal stem cells. Treatment of grafts with gelatine or fibronectin improved colonization of grafts with cells.

The olfactory epithelium (OE) is an accessible source of neural stem cells and progenitor cells. The objective of the study was to compare the effectiveness of various biopsy sites to isolate and propagate neural progenitor cells from the olfactory epithelium (OE). The authors assessed OE cell count in OE in different sites of the nasal cavity and showed the possibility of isolation neurospheres from nasal biopsies. In total, 45 inpatinets were included in the study. Biopsy specimens were obtained from 30 patients undergoing septoplasty and/or turbinate surgery. Three areas of OE were biopsied: lower third section of the nasal septum (A), anterior part of the middle turbinate (B), upper third of the nasal septum (C). Immunocytochemistry and fluorescence-activated cell sorting showed that OE cells were NCAM-positive. Mean percentage of NCAM+ cells was 7.8% for A, 42.7% for B and 18.2% for C. The difference was significant between A and B (p=0.0001) and B and C (p=0.01). Therefore, the anterior part of the middle turbinate was an easily accessible and safe site to obtain neural cells. To confirm this, neurospheres were obtained in 15 patients with schizophrenia who underwent in-office endoscopy.

MiR-222-3р has been implicated in tumor cell proliferation and has an important role in the differentiation and maturation of myogenic cells. However, its role in skeletal myoblast proliferation is still unclear. In this study, we found that miR-222-3р expression increases initially and then decreases during C2C12 myoblast proliferation. Using synthetic miRNA mimics and inhibitors in gain- or loss-of-function experiments, we snowed that miR-222-3р overexpression in C2C12 cells promotes myoblast proliferation and represses myofiber formation, while miR-222-3р downregulation has the opposite effect. Using a prediction program, BTG2 was identified as a possible target gene of miR-222-3р. During myogenesis, miR-222-3р mimics repress BTG2 expression, while miR-222-3р inhibitors promote BTG2 expression. Using dual-luciferase reporter assay, we further demonstrated that miR-222-3р specifically targets BTG2. Additionally, we show that siRNA-mediated downregulation of BTG2 expression in C2C12 myoblasts promotes the proliferation and suppresses differentiation. In conclusion, we provide a novel insight into the mechanism by which miR-222-3р regulates the proliferation and differentiation of C2C12 myoblasts by targeting BTG2. This information contributes to our understanding of the role of miRNAs in skeletal muscle development.

This review analyzes three studies carried out on Drosophila, which resulted in discoveries that would be impossible while using other subjects. Thanks to these discoveries, events accompanying the myoblast fusion process, the oocyte polarization, and the functioning of supracellular linear actomyosin cable-like structures coordinating the polarization of the cytoskeleton of the cell can be described in detail.

The paper gives the current data available in the literature on the relationship and pathogenetic mechanisms of influence of adipose tissue on colorectal carcinogenesis. It considers the aspects of changes in adipose tissue and microenvironment of the tumor itself, including those under the influence of biologically active substances secreted by adipocytes; differences in subcutaneous and visceral fat and their importance in the development and progression of colorectal cancer (CRC), as well as the role of adipose tissue-derived stem cells. Understanding these mechanisms for adipose tissue influence on CRC will assist not only in preventing this disease, but also in searching for new therapeutic targets.

The work describes the development of a reagent kit for high-performance HLA-typing using the Illumina MiSeq System platform. The developed reagent kit contains all the necessary components for target enrichment of five HLA genes, preparation of libraries, and software for automatic data analysis. The reagent kit verified on a 93 DNA samples with known genotypes. During the verification, the sensitivity and specificity of the reagent kit for each of the HLA loci were determined - for A and B they were 1.0 and 1.0, respectively, for the C-1.0 and 0.99 locus, for the DRB1 locus 0.98 and 0.99, for the DQB1 locus 0.98 and 0.93.