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Vol 15, No 4 (2020)

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Open Access Open Access
Restricted Access Access granted
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On the current status and prospects for the development of clinically significant cell technologies: do not interfere!

Mentkevich G.L., Isaev A.A., Prikhodko A.V., Potapov I.V., Deev R.V.


The material contains a conversation between doctors-developers, administrators and clinicians on the introduction of banking of umbilical cord blood and umbilical cord cells into healthcare practice. The data on clinical studies conducted in the world to assess the safety and effectiveness of the use of umbilical cord blood cells are presented.
Genes & Cells. 2020;15(4):6-13
pages 6-13 views

Professor Andrey Pavlovich Dyban in memoirs of the members off the staff of the department of embryology of the University of Warsaw

Tarkowski A.K., Dyban P.A.


The article provides information about the life and creative path of academician A.K. Tarkowski (Poland) and professor A.P. Dyban (USSR-Russia). The memories of academician A.K. Tarkowski about his friendly relations with professor A.P. Dyban are very valuable for understanding the era, when it was necessary to overcome significant difficulties and barriers that hindered scientific communication between scientists from different countries. The memories characterize not only professor A.P. Dyban, but also are of considerable interest for understanding the uniqueness of the personality academician A.K. Tarkowski: his benevolence, observation skills, intelligence, his subtle humor.
Genes & Cells. 2020;15(4):14-18
pages 14-18 views

Immunotherapeutic approaches in the treatment of COVID-19

Abakushina E.V.


The novel coronavirus SARS-CoV-2 has caused a life-threatening disease COVID-19 provoked a pandemic over the world. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of pro-inflammatory cytokines "cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact immunophysiology and treatment, especially for the severe COVID-19, is still uncertain. Novel therapeutic strategies are urgently needed to eliminate the viral reservoir in the host. In this review, we described several potential strategies for immunotherapy to cure SARS-CoV-2 infection. This may provide clue of using immune therapy as combine treatment to prevent the patient develop into severe respiratory syndrome and largely reduced complications.
Genes & Cells. 2020;15(4):19-26
pages 19-26 views

Participation of adhesion molecules in changing cell interactions during metastasis development

Shevlyuk N.N., Khalikova L.V., Khalikov A.A., Bakeev M.R., Lipatov D.O., Mustafin R.N.


The review summarizes current information about the role and significance of adhesion molecules in the process of tumor metastasis. For example, different tumors is shown that changes in the expression of adhesion molecules leads to disruption of the regulatory interactions in the processes of proliferation, cytodifferentiation and migration of tumor cells, enables the cascade of pathological processes leading to the colonization of other tumor cells remote from the tumor bodies. The phenomenology of tumor development and metastasis is shown. The participation of the main groups of adhesion molecules (cadherins, integrins, selectins, immunoglobulins and white blood cell homing receptors) at the stages of metastasis is considered. A violation of cadherin expression is accompanied by a decrease in the expression of integrins involved in the formation of hemidesmosomes, while a cascade of reactions develops that contributes to the development of an aggressive malignant phenotype, cells acquire an increased ability to migrate and invade, resulting in the appearance of a tumor in secondary foci. The role of immunoglobulins in the development of metastatic process has been studied in less detail than in cadherins and integrins. It was found that immunoglobulins are involved in the formation of resistance of tumor cells to proapoptotic signals. Immunoglobulins increase the expression of metalloproteinase genes involved in the degradation of the extracellular matrix, which is a factor in the initiation of metastasis. A correlation between increased selectin expression and increased metastasis is shown. An increase in the expression level of white blood cell homing receptors leads to an increase in the invasive potential of tumors. The results of the study of cell adhesion proteins serve as a fundamental basis for the development of methods of antitumor therapy. Over the past decades, a number of immunohistochemical protein detection reactions have become one of the diagnostic methods of cancer clinics. However, the role of cell adhesion molecules in ensuring the metastasis process, as well as their significance in the prognosis of the development of the tumor process and antitumor therapy, needs to be further studied.
Genes & Cells. 2020;15(4):27-32
pages 27-32 views

Non-viral delivery of the BMP2 gene for bone regeneration

Nedorubova I.A., Bukharova T.B., Vasilyev A.V., Goldshtein D.V., Kulakov A.A.


Gene-activated bone grafts and substitutes are promising tools for the bone defect healing, which are capable to induce prolonged production of growth factors with a therapeutic effect at physiological concentrations. Non-viral methods of delivering plasmid constructs with target genes are the safest for clinical use, but their efficiency is lower in comparison with viral vectors. To solve the problem of plasmid delivery into cells, some systems with a high transfection capacity and ensure sufficient cell viability are being developed. Moreover, there are different approaches to improve the level of expression of target genes and targeted delivery to the bone defect in order to achieve local therapeutic concentrations. This review considers approaches which are aimed to increase the efficiency of bone tissue regeneration methods based on non-viral delivery systems for osteoinduction genes using the example of the bone morphogenetic protein-2 gene.
Genes & Cells. 2020;15(4):33-39
pages 33-39 views

Study of the RS2910164 polymorphic variant of MIR-146A microRNA gene in patients with primary osteoporosis

Yalaev B.I., Khusainova R.I.


MiRNAs, known as the family of short non-coding RNAs, are key repressors of gene expression and play an important role in the regulation of osteogenesis, interact with signaling molecules of bone remodeling, and control the processes of differentiation of bone cells. A study of the polymorphic variant rs2910164 (n. 303C>G) of the microRNA gene (miR-146a) and an assessment of its role in the formation of the risk of osteoporetic fractures and low bone mineral density (BMD) in a sample of postmenopausal women and men over 45 years of age was conducted. The C allele was found to be associated with a low level of bone mineral density in the lumbar spine in women. There were no significant associations of the studied locus with osteoporotic fractures in General and their separate localities in men and women, with a low level of BMD in General and various localities in men.
Genes & Cells. 2020;15(4):40-45
pages 40-45 views

Serum cytokine profile indicators after subcutaneous implantation of the decellularized esophagus matrix in rats

Melkonyan K.I., Nakokhov R.Z., Rusinova T.V., Kozmai Y.A., Bykov I.M., Redko A.N., Alekseenko S.N.


Study of postimplantation immune response to decellularized matrices has great importance for assessing biocompatibility of tissue-engineered structures based on them, since inflammatory process and excessive production of inflammatory mediators lead to complications and implant rejection. The aim of this research: serum cytokine profile studying after subcutaneous implantation of decellularized esophagus matrix in rats. Experimental data were obtained on male Wistar rats aged 5-6 months (n=55). Rats were divided into 4 groups: two control groups, experimental and comparison group. Control group 1 consisted of conditionally healthy rats (n=10), control group 2 - shame-operated animals (incision in scapula without implantation, n=15). In experimental group (n=15), rats underwent subcutaneous implantation of decellularized esophagus fragments; in group 2 (n=15) - native esophagus fragments. Peripheral blood sampling and fragment explantation were performed on 7th, 14th and 21st experimental days. Serum samples were tested for IL1a, IL2, IL4, IL17A, TNFa, IFNy, GM-CSF content by ELISA. Explanted native esophagus and decellularized esophagus fragments were subjected to histological analysis. On 7th experimental day, significant increase in IL1 a content was observed in rats with implantation of decellularized esophagus fragments. IL17A, IFNy, GM-CSF content significantly decreased. On 14th day, IL17A concentration sharply decreased in comparison with value on 7th experimental day and control 1. IL1 a and IFNy concentration decreased in comparison with control group 1 values and 7th day respectively. On 21st day, dynamics of decrease in IL17A, IFNy, IL1 a content in this rat group was revealed. Thus, it was found change in concentrations of studied cytokines corresponds to regeneration histomorphological picture in group that underwent implantation of acellular matrices against of active inflammatory reaction in comparison group. Concentrations of IL1 a, IL4, IL17A, IFNy reflect positive dynamics of wound healing process and absence of decellularized matrix rejection.
Genes & Cells. 2020;15(4):46-56
pages 46-56 views

Effects of inhibition of glycogen synthase kinase 3p on neuromuscular synaptic transmission in transgenic mice with model of alzheimer's disease

Mukhamedyarov M.A., Grigoryev P.N., Ushanova E.A., Zefirov A.L.


Alzheimer's disease is the most common neurodegenera-tive disease. Synaptic dysfunction plays important role in pathogenesis of Alzheimer's disease. Recently, glycogen synthase kinase 3 has been considered as a potential target for therapy of Alzheimer's disease, since the activity of this enzyme, which regulates many cellular and synaptic functions, is impaired in this pathology. In this paper, we studied the effects of inhibition of glycogen synthase kinase 3p on the parameters of the peripheral (neuromuscular) synapse functioning in the Alzheimer's disease model in APP/PS1 transgenic mice. In electrophysiological experiments on the diaphragm of APP/PS1 of mice, application of the glycogen synthase kinase 3p inhibitor AR-A014418 (1 pM) did not cause significant changes in the parameters of spontaneous and evoked neurotransmitter release, as well as in the dynamics of the amplitude of the end-plate potentials during high-frequency stimulation. In fluorescent experiments using the dye FM 1-43, it was found that the application of AR-A014418 (1 pM) does not significantly change the intensity of endocytosis, but causes moderate enhancement of exocytosis of synaptic vesicles during high-frequency stimulation. Enhancement of synaptic vesicle exocytosis due to inhibition of glycogen synthase kinase 3p may alleviate neuromuscular synaptic dysfunction in APP/PS1 mice. The obtained results can be used in studies aimed to development of therapeutic strategies for Alzheimer's disease.
Genes & Cells. 2020;15(4):57-60
pages 57-60 views

Results of a comparative valuation of the efficiency of using the plasmid construct pBud-VEGF165-FGF2 in models of autograft of the sciatic nerve defect and tubulation with the NeuraGen® collagen tube

Masgutov R.F., Masgutova G.A., Mukhametova L.R., Idrisova K.F., Mullakhmetova A.F., Syromiatnikova V.Y., Bogov A.A., Salafutdinov I.I., Arkhipova S.S., Salikhov R.Z., Rizvanov A.A.


Traumatic injuries of peripheral nerves lead to profound disability in patients with partial or total loss of limb function. There remains the question about the use of technologies for detecting defects of the peripheral nerve with concurrent of its regeneration. In the study it has been investigated the effect of the gene-therapeutic plasmid construct pBud-VEGF165-FGF2 with various methods of overcoming 5 mm diastasis of the sciatic nerve: nerve autograft and tubulation with the NeuraGen® tube. In the study groups, assessment of sciatic nerve regeneration was based on functional and morphometric parameters. Direct injection of plasmid pBud-VEGF165-FGF2 stimulates regeneration and restoration of motor function in both groups, but with different efficacy. Comparative analysis of nerve defect replacement in combination with direct gene therapy showed the most effective approach with autologous insertion replacement by comparison to the NeuraGen. Thus, on the basis of the obtained data, we can assert that nerve autograft of the peripheral nerve remains the "gold standard” and provides the best hope of research in combination with the use of various regeneration stimulants.
Genes & Cells. 2020;15(4):61-65
pages 61-65 views

Pilot study of bone tissue reparative regeneration of the young Trachemys scripta shell

Deev R.V., Podluzhnyi P.S., Galkov S.S., Chernoraev A.V.


The turtles skeleton plan is an evolutionary developmental novelty in connection with the formation of a tortoise-specific carapacial ridge, which induces the growth of ribs in the dorsal direction and the subsequent formation of several carapace plates. The bone plates of these reptiles have different histogenesis: the neural and costal plates develop according to the mechanism of indirect osteogenesis by perichondral ossification of the axial skeleton elements (vertebrae and ribs), the peripheral and plastron bones develop according to the mechanism of direct osteogenesis in the dermis of the skin - these are the so-called «skin bones», which are derived from individual osteogenic cells outside the axial skeleton and develop by intramembranous osteogenesis. An experiment was carried out to study the post-traumatic osteogenesis of the carapace bone plates on a freshwater turtles Trachemys scripta at the age of 3 months. Two defects of carapace costal plates with a diameter of 4 mm and a depth to the fascia were performed with further routine histological examination. It was found that already on the 90th day the turtles carapace bones were restored with the formation of a full-fledged bone regenerate by the mechanism of indirect osteogenesis.
Genes & Cells. 2020;15(4):66-69
pages 66-69 views

Genetic diagnostics and treatment of young adult acute myelomonoblastic leukemia patient using double haploidentic bone marrow transplantation

Vinogradov A.V., Izotov D.V., Rezaykin A.V., Anisimova I.V., Konstantinova T.S., Kudryashova A.V., Sazonov S.V., Sergeev A.G.


Treatment ofprognostically unfavorable forms ofacute leukemia isaserious problem ofhematology, since their frequency inthe group ofadult patients reaches 60%, and inelderly patients- 80-90%.Aim: toanalyze the case ofdiagnostics and treatment ofacute myelomonoblastic leukemia with anunfavorable genetic prognosis inayoung adult female using double haploidentical bone marrow transplantation.Samples ofbone marrow and peripheral blood ofpatient K., 35years old, who recived program chemotherapy and double haploidentical bone marrow transplantation inthe Sverdlovsk Regional Hematological Centre were examined.Atthe onset ofdisease was noted hyperleukocytosis, blastaemia and infiltration ofleukemic cells inthe bone marrow. Cytochemical reactions tolipids were positive in7,0% ofblasts, small-granular and large-granular glycogen was detected in24,0% ofblast cells, and diffuse- in22,0%. Immunophenotypically, 28,0% ofblast cells were characterized byexpression ofHLA-DR, CD13, CD33, CD34, CD38, CD117, MPO-cyt, 13,0%- CD33, CD11cyt, CD64, CD14. The cytogenetic study determined the karyotype 48, XX, +4, +21[2]/ 47, XX, +4[3]/ 46, XX[2]. Non-synonymous transversions с. 2447A>Тinс-KIT gene, с.215С>GinТР53, and transition с. 2644С>ТinDNMT3A were detected using direct sequencing method. Despite the detection ofoncogenic mutations, the tumor was chemosensitive topolychemotherapy (including anthracyclines with cytarabine). However, given the unfavorable genetic prognosis, itwas decided toperform abone marrow transplantation. Due tothe lack ofanHLA-matched unrelated donor, the first haploidentical transplantation was performed from the patient'seldest daughter. At+51day, transfusion ofdonor white blood cells with correction ofthe immunosuppression scheme was performed tocorrect persistent pancytopenia. At+ 71day after the first transplantation, taking into account the remaining pancytopenia, asecond haploidentic transplantation from the patient'syounger daughter was performed. The total duration ofhematological remission was 48months, including 36months after the second haploidentical bone marrow transplantation.
Genes & Cells. 2020;15(4):70-74
pages 70-74 views

Role of the immune system in COVID-19 pathomorphogenesis

Studenikina E.D., Ogorelysheva A.I., Ruzov Y.S., Khabibullin I.R., Samorukova I.Z., Chernova O.N., Asaulenko Z.P., Mavlikeev M.O., Budnicova I.N., Nikolaev V.I., Vinnichuk S.A., Deev R.V.


The new coronavirus infection is a highly contagious infection caused by the SARS-CoV-2 virus that has become a global public health problem. The pathogenesis of this virus has not yet been clearly understood, the principles of hyperinflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome and multiple organ failure, innate and adaptive immune responses in the process of structuring the data under study. The interaction of the virus and a macroorganism includes 4 stages: infection, dissemination, cytokine storm, pulmonary fibrosis. This review analyzes the predictors of infection, its possible pathogenesis, the immune response of the macroorganism, as well as the histological characteristics of damage to immune organs; shows receptors for SARS-CoV-2 (ACE2, TMPRSS2) in some organs.
Genes & Cells. 2020;15(4):75-87
pages 75-87 views

Analysis of the legal regulation of the use of umbilical cord blood and its components in the Russian Federation and abroad

Litvinova L.S., Goncharov A.G., Shupletsova V.V., Gazatova N.D., Melashchenko O.B., Yurova K.A., Pestrikova A.A.


Umbilical cord blood is a unique source of hematopoietic cells for transplantation in hematological diseases and other socially significant pathologies. The development of regenerative medicine requires clear protocols governing the use of umbilical cord blood and its components (cells, plasma) in clinical practice. In the Russian Federation, today, there is no proper regulatory framework for working with umbilical cord blood and its components, which is a limiting factor in the development of cellular technologies and regenerative medicine in general. The article analyzes the legal framework for regulating the use of umbilical cord blood and its components in the Russian Federation and abroad - the countries of the European Union and America.
Genes & Cells. 2020;15(4):88-94
pages 88-94 views

Instructions for authors

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Genes & Cells. 2020;15(4):95-97
pages 95-97 views

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