Vol 14, No 1 (2019)

Full Issue


Microglia histogenesis: the history of research

Deev R.V., Dikonenko M.V., Grechanik U.P.


The researches of histogenesis and histophysiology of microglia and its role in evolution of central nervous system pathology attract less attention than it should. The proposed review is devoted to the problem of microglia's origin and history of microglia research. Various number of hypotheses concerning microglia histogenesis were suggested in different periods, specifically the hypothesis about ectodermal or mesodermal (mesenchymal) histogenesis of microglia and its origin. This review represents the role of domestic and international histologists in study of microglia histogenesis, especially the role of professor Beletskiy.
Genes & Cells. 2019;14(1):6-15
pages 6-15 views

Gene-activated hydrogels in regenerative medicine

Bozo I.Y., Bilyalov A.I., Mavlikeev M.O., Deev R.V.


Hydrogels capable to optimize reparative regeneration and delivere biologically active components (drugs, cells, growth factors, gene constructs) in the implantation area are attracting increasing attention of developers due to high potential effectiveness of these medical devices and compliance of the approach with well-known medical trend - minimally invasive technologies. Hydrogels containing gene constructs have become especially relevant for clinical practice in the territory of the Eurasian Customs Union after gen-therapeutic drug and the first gene-activated bone substitute were registered in Russia. This review describes the main directions in development of gene-activated hydrogels divided into two categories: primitive and optimized ("smart”-hydrogels). In the case hydrogel scaffolds provide passive delivery of gene constructs, while the latter facilitate gene constructs to realize their mechanism of action.
Genes & Cells. 2019;14(1):16-21
pages 16-21 views

The research of the molecular mechanisms of endothelial dysfunction in vitro

Kalinin R.E., Suchkov I.A., Korotkova N.V., Mzhavanadze N.D.


Endothelial dysfunction is universally regarded as one of the key elements in the pathogenesis of most of cardiovascular diseases including ischemic heart disease, atherosclerosis, arterial hypertension, myocardial infarction, stroke, dilated cardiomyopathy, as well as diabetes mellitus, inflammatory, oncological, and autoimmune diseases. Localization of endothelial cells in tunica intima of the vessels limits in vivo analysis of the intracellular proteins and other molecules, which regulate cellular functional activity. A possible solution to this problem may be setting experimental conditions for physiological and pathological functioning of endothelial cells. In vitro modeling of endothelial dysfunction may be a useful tool for the development of methods to improve the endothelial function and evaluate the effects of medicinal products. The objective of this literature review is to summarize main trends in studying endothelial dysfunction in vitro using different endothelial cell cultures.
Genes & Cells. 2019;14(1):22-32
pages 22-32 views

Astrocytes and their participation in the mechanisms of therapeutic action of MSC in ischemic brain injury

Kalinina Y.A., Gilerovich E.G., Korzhevskii D.E.


This review summarizes data on the role of astrocytes in the normal brain function and disease. After ischemic injury astroglia participates in the processes of endogenous repair and helps the surviving nerve cells to regain their lost functions. The response of astrocytes to ischemia depends on the severity of the disease and can determine its further development. To date, cellular therapy is a promising strategy in the treatment of post-stroke states. Numerous studies have shown the positive effect of mesenchymal stem cells (MSC) on functional recovery after ischemic stroke. The main effect is probably associated to the ability of MSC to enhance the endogenous restoration potential of nerve tissue. Recent experimental data have demonstrated that a special role in the therapeutic effects of cell therapy belongs to astroglial cells. Further study of the interaction of MSC and astrocytes will help in the search for new approaches in the treatment of the ischemic injury consequences.
Genes & Cells. 2019;14(1):33-40
pages 33-40 views

MicroRNAs in the regulation of osteogenesis in vitro and in vivo: from fundamental mechanisms to bone diseases pathogenesis

Galitsyna E.V., Bukharova T.B., Vasilyev A.V., Goldshtein D.V.


The review examined the participation of microRNA in the posttranscriptional regulation of the genes of the two main signaling pathways of osteogenic differentiation - canonical BMP/ SMAD and WNT/p-catenin. The positive and negative effects of microRNA on osteogenic differentiation in various cell cultures of humans and animals, including the choice of directions between adipo-, chondro- and osteogenesis, are indicated. The role of miRNA in the pathogenesis of bone tissue diseases and the prospects for developing methods for their diagnosis and therapy are described.
Genes & Cells. 2019;14(1):41-48
pages 41-48 views

Genetic heterogenety of tumour-like lesions of bones in maxillofacial area

Sviridov E.G., Kadykova A.I., Redko N.A., Drobyshev A.Y., Deev R.V.


Benign tumors and tumor-like lesions of the bones are rare. At present, their diagnosis is based on radiation and pathological methods. However, the genetic etiology of this group of diseases is being actively studied in order to search for molecular markers with high diagnostic and prognostic potential.
Genes & Cells. 2019;14(1):49-54
pages 49-54 views

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

Radzhabova A.M., Voloshin S.V., Martynkevich I.S., Kuzyaeva A.A., Shuvaev V., Motyko E.V., Kuvshinov A.Y., Fominykh M.S., Schmidt A.V., Polushkina L.B., Bakay M.P., Tiranova S.A., Zenina M.N., Potihonova N.A., Kudryashova S., Balashova V.A., Chubukina J.V., Uspenskaya O.S., Karyagina E.V., Bogdanov A.N., Chechetkin A.V.


Detection of FLT3 gene mutations in acute myeloid leukemia is now recognized as an unfavorable factor that affects the disease course, emerging the risk of relapses and overall survival shortening and disease-free survival of patients. The aim of the study was to determine the frequency of mutations of the gene FLT3 and to assess their impact on clinical indicators, overall survival and disease-free survival in patients with acute myeloid leukemia. We compared complete blood count parameters, karyotype, duration of overall survival and disease-free survival in 199 patients with acute myeloid leukemia depending on the presence or absence of mutations of the FLT3 gene. Significant differences across these groups were discovered only in WBC and blasts between the group of patients with acute myeloid leukemia (FLT3+) and without mutations in the FLT3 gene (FLT3-). The differences between two groups were also identified in patients chromosomal aberrations. Significant differences (p=0,00024) in the duration of overall survival between groups of patients with acute myeloid leukemia with mutations of FLT3-ITD+, FLT3-TKD+ and FLT3- were demonstrated. Median overall survival was: 1 6 months for patients with mutation FLT3-ITD+ and 17 months for FLT3-TKD+ patients and not achieved for FLT3- patients. The use of modern molecular genetic methods of research in acute myeloid leukemia allows to improve the diagnosis of the disease, as well as to carry out risk stratification and individualize therapy. The use of targeted therapy for FLT3-positive patients who are not candidates for hematopoietic stem cell transplantation will increase the effectiveness of the treatment and improve the performance of overall survival and disease-free survival.
Genes & Cells. 2019;14(1):55-61
pages 55-61 views

Ultrastructural comparative analysis of neuroendocrine tumors of pancreas

Chekmareva I.A., Paklina O.V., Gordienko E.N., Kaldarov A.R.


Detection of ultrastructural distinctions of tumor cells and cell-to-cell cooperation in insulinomas and nonfunctioning neuroendocrine tumors of pancreas. Ultrastructural study of 38 insulinomas and 35 nonfunctioning neuroendocrine tumors of pancreas of the patients treated at Vishnevskiy Surgery Institute from 2010 to 2015. Insulinomas are characterized by high differentiation of intracellular organelles and specific secretory granules. In insulinomas the number of immature endocrine granules exceeded the number of mature granules. The tumor cells were often joined together and held with desmosomes ensuring very tight connection. Desmosome complexes were characterized by their extended length. Such ultrastructural changes were not followed by destruction of tumor cells. There was formation of specific syncytium-like structures consisting of cells connected by cytoplasmic channels with the common cytoplasm with cell organelles. In nonfunctioning tumors the most of the granules were distinguished by polymorphism and had no specific ultrastructure indicating the synthesized hormone. In large areas there were loss of plasmolemma integrity, up to its complete absence, which led to unification of cytoplasmic contents of the cells. Common junctions dominated in nonfunctioning tumors. Desmosomes were rare, poorly developed, and in the form of immature and reduced junctions. Complex cellular junctions are well developed in the cells, ensuring tight connection of tumor cells, reducing their invasive and metastatic potential. Nonfunctioning neuroendocrine tumors on the contrary are characterized by underdevelopment of cellular organelles and immaturity of secretory granules. Predominance of weak direct cell junctions, rupture of membranes of neighboring cells with simultaneous reduction of desmosomes facilitate the migration of individual tumor cells and formation of metastases.
Genes & Cells. 2019;14(1):62-67
pages 62-67 views

Vascular endothelial growth factor in tissues of patients with IHD, before and after coronary bypass surgery

Shevchenko Y.L., Borshchev G.G., Fomina V.S., Kim K.F.


We present the comparative results of the study of endothelial growth factor (VEGF) in the tissues of patients with and without coronary artery disease. Concentration of the investigated growth factor was found to be higher in tissues of patients with IHD (p<0.05). Identified high content of VEGF in adipose tissue of involutive thymus and epicardial adipose tissue was stable (without signs of decreasing concentration for 3 days). Among the potential sources of VEGF, the fluid aspirated from the drains in patients on 1 day after open myocardial revascularization was proposed. Removal of blood corpuscle from the liquid did not significantly reduce the concentration of VEGF (p>0.05), but decreased the total volume of the liquid by almost 4 times (p<0.05).
Genes & Cells. 2019;14(1):68-71
pages 68-71 views

Amyotrophic lateral sclerosis: characteristics of the immunophenotype of hematopoietic precursor cells as a potential biomarker for early diagnostics of fatal disease

Bryukhovetskiy A.S., Grivtsova L.Y.


Amyotrophic lateral sclerosis also known as motor neuron disease is a fatal neurodegenerative disease that manifests by degeneration of motor neurons, hypotrophy and atrophy of the muscles. The causes and pathogenesis of amyotrophic lateral sclerosis are not clear so far, the effective therapy is absent. Amyotrophic lateral sclerosis is diagnosed by clinical and neurophysiologic examination and only when over 80% of motor neurons are dead. The multiparameter flow cytometry was used to evaluate the expression of HLA-DR, CD38, CD117, CD13, CD33, CD56, CD90, CD45, CD10, CD71 in 86 samples of the mobilized hematopoietic stem cells from 54 amyotrophic lateral sclerosis cases and in 61 samples of mobilized hematopoietic stem cells from 54 healthy donors. The analysis showed differences in the hematopoietic stem cells subpopulations of amyotrophic lateral sclerosis donors as compared to those of healthy donors and allowed for the introduction of the notion of the amyotrophic lateral sclerosis-specific immu-nophenotypic profile of hematopoietic stem cells membrane antigens. The profile allows for verification of neurospecific immune insufficiency at the level of progenitor cells of the bone marrow and diagnostics of the family and sporadic amyotrophic lateral sclerosis in a molecular-biological way at the earliest stage before clinical manifestation of the disease. We suppose that the amyotrophic lateral sclerosis makes its debut as the disease of hematopoietic stem cells and manifests as pathologic changes at the level of hematopoietic stem cells genome and proteome that are represented in the subpopulation composition of hematopoietic stem cells and their immunophenotypic characteristics, becoming the cause of genetically determined genuine autoimmune origin of the disease so that the motor neuron disease manifests only in the end. However, further research with larger samples and experimental check of the evidence is required.
Genes & Cells. 2019;14(1):72-79
pages 72-79 views

Reserve and basal cells of epithelia of cervix uteri as a source of cervical neoplasies by human papilloma viruses

Ershov V.A., Mikhailov V.M., Chirsky V.S.


As progenitor of cervical epithelium consider reserve and basal cells. They as human stem cells possess ability of self-updating, manufacture of the differentiated functional posterity and settle down in a niche. They supports the population by means of mitosis. For a reserve cell it is characteristic expression p63, bcl-2, keratins 5, 7, 17, for basal cells - p63, bcl-2, keratins 5, 7, 10, 13, 14, 17. Reserve cells are a source of development of columnar and squamous epithelia of cervix uteri, basal cells - only squamous epithelium. Reserve and basal cells are cells-targets for human papilloma virus (HPV) which genetic changes can serve as the reason can-cerogenesis. For "precancerous” cervical intraepithelial neoplasies in prevailing number of supervision spontaneous regress is characteristic. The role of integration of DNA HPV in cancerogenesis of cervix uteri does not find unequivocal acknowledgement in DNA of a cell. Modern representations about cancer stem cell of cervix uteri characterize its similarity to stem cells of cervical epithelium.
Genes & Cells. 2019;14(1):80-84
pages 80-84 views

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