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Vol 13, No 1 (2018)

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Modern ideas about cell death

Deev R.V., Bilyalov A.I., Zhampeisov T.M.


Cell death is an important part of normal (physiological) and pathological histogenesis. In the past two decades, our knowledge of the processes of non-programmed and programmed cell death significantly enriched. The International Nomenclature Committee on Cell Death is constantly working, it regularly updates information on the terminology and development mechanisms recommended for this or that type of death, but the general principle of classification of cell death has not yet been worked out. In this review, the principle of separation according to which the mechanisms involved in physiological histogenesis include the rooting, the external pathway of apoptosis, anoikis, macroautophagy and lysosome-dependent cell death. The mechanisms involved in pathological histogenesis include: the internal pathway of apoptosis, necroptosis, pyroptosis, netosis, mitotic catastrophe, partanatosis, entosis, mitochondrial-driven necrosis, ferroptosis, immunogenic cell death, necrosis and oncosis.
Genes & Cells. 2018;13(1):6-19
pages 6-19 views

Bone marrow stem cells for the critical limb ischemia treatment: biological aspects and clinical application

Orekhov P.Y., Konoplyannikov M., Baklaushev V.P., Kalsin V.A., Averyanov A.V., Konopliannikov A.G., Habazov R.I., Troitskiy A.V.


Cell therapy is one of the most promising directions in the treatment of critical limb ischemia (CLI). In spite of certain advances achieved in this field in the last decades, which are related to application of bone marrow stem cells (BMSC), a large number of problems still remain unsolved. In this review, we discuss the BMSC biology, mechanisms of their therapeutic effect in the CLI treatment and results of the most notable BMSC-based clinical studies in detail.
Genes & Cells. 2018;13(1):20-34
pages 20-34 views

OMICS technologies in reproductive medicine: assessment of quality of oocytes and embryos

Zhiryaeva E.A., Kiyasova E.V., Rizvanov A.A.


One of the main factors of success of the procedure art (assisted reproductive technology) is the selection of the most "high-quality” gametes for further manipulation and obtaining a viable embryo for implantation. The majority of modern techniques based on morphokinetic predictors of quality (i. e. assessment of embryo morphology and rate of division of the blastomeres), which allowed to achieve some success in increasing the percentage of successful pregnancies and reduce the number of multiple pregnancies, but their accuracy is currently insufficient. Thus, the development of objective, reliable, fast and affordable test systems to determine the quality of oocytes and the development potential of the embryo - one of the challenges of reproductive medicine. The purpose of this review was to describe the advantages and limitations obecnych technologies, the application of which will allow to deepen our understanding of the physiology of the embryo, as well as set criteria for non-invasive selection of gametes and embryos. In this regard, recently in assisted reproduction are applied the studies of genomic, proteomic, transcript, and metabolomic profiles of oocytes, granulosa and Cumulus cells, embryos, of conditioned media.
Genes & Cells. 2018;13(1):35-41
pages 35-41 views

Peculiarities of non-coding RNA functioning in the norm and cerebral ischemia

Filippenkov I.B., Limborska S.A., Dergunova L.V.


To date, it has been shown that not only information RNAs, but also various types of non-coding RNA, are involved in the transcriptome reaction in ischemia. In particular, non-coding RNAs can perform important protective functions, acting as competitive endogenous RNAs. They interact with microRNA, which negatively affects the expression of many mRNAs, and neutralize their activity. The particular interest is circular RNAs, which belong to the non-coding RNAs and can most effectively perform the functions of competitive RNAs. Circular RNAs demonstrate the increased resistance to exonucleases and the predominant brain-specific expression pattern, which may indicate their particular importance in this tissue as neuroprotective agents. This review demonstrates the most recent data on the structure and features of the functioning of noncoding RNAs, which indicate the important role of circular RNAs in cell in the norm and ischemia conditions.
Genes & Cells. 2018;13(1):42-46
pages 42-46 views

Alcohol and Immunity

Gazatova N.D., Yurova K.A., Gavrilov D.V., Litvinova L.S.


The review systematizes data characterizing the impact of moderate and excessive alcohol consumption on the immune system of humans and animals. In particular, the results of experimental and clinical studies on the effect of ethanol on the function of cells of congenital and adaptive immunity are presented, depending on the dose and duration of its exposure, which affects the response of the organism to agents of an infectious and non-infectious nature. The issues of chronic lymphopenia induced by chronic alcohol consumption are discussed in detail, which leads to a decrease in the number of naive lymphocytes in circulation. The dose-dependent and temporary effects of alcohol on the functional activity and homeostasis of immune cells of the central nervous system (CNS), in particular, astrocytes and microglia, are considered. In general, the review analyzed a complex of complex interactions between ethanol, its metabolites and functional activity of the hypothalamic-pituitary-adrenal system and the immune system.
Genes & Cells. 2018;13(1):47-55
pages 47-55 views

Efficacy of combined use of plasmid constructs containing HGF and angiopoietin-1 genes to restore blood flow in ischemic tissues

Rubina K.A., Semina E.V., Diykanov D.T., Boldyreva M.A., Makarevich P.I., Parfyonova Y.V., Akopyan Z.A., Tkachuk V.A.


New methods to stimulate blood supply of the ischemic organs and tissues are being intensively developed worldwide. These approaches are based on revascularization and remodeling of the newly formed blood vessels. This strategy was called therapeutic angiogenesis. Using in vitro, ex vivo and in vivo models we investigated the specific biological activity and angiogenic potential of Vascopoietin, which contained the plasmids for HGF and angiopoietin-1 expression. Vascopoietin stimulated vascular cell migration, proliferation and the formation of capillary-like structures in vitro and ex vivo. Using in vivo model of posterior limb ischemia in mice we demonstrated that Vascopoietin administration mediated stable HGF and angiopoietin-1 production resulting in new blood vessel formation and their stabilization in the ischemic muscles. In addition, Vascopoietin injection led to the restoration of the blood flow, decrease in the size of necrosis in ischemic limb and the reduction in the amputation frequency. The current data suggest Vascopoietin a promising drug for therapeutic angiogenesis.
Genes & Cells. 2018;13(1):56-64
pages 56-64 views

Interleukin-8 is able to promote pro-inflammatory activity of human monocytes (macrophages)

Meniailo M.E., Malashchenko V.V., Shmarov V.A., Gazatova N.D., Melashchenko O.B., Goncharov A.G., Seledtsova G.V., Seledtsov V.I.


Interleukin-8 (IL-8, CXCL8) is one of the main chemokines that stimulates the migration of neutrophils, monocytes and lymphocytes into the inflammatory focus. The aim of this study was to investigate the direct influence of IL-8 on the functionality of human monocytes/macrophages (Mc (Mph)) upon their activation by lipopolysaccharide (LPS). CD14+ cells were isolated from blood mononuclear cells (MNCs) by positive magnetic separation. Surface markers (CD16, CD119, CD124, CD197) in Mc (Mph) cultures were determined by flow cytometry, while IL-10, IL-6, IL-1 ß and tumor necrosis factor-а (TNF-а) concentrations in cell supernatants by solid-phase enzyme-linked immunosorbent assay. IL-8 was found to be capable of significantly reducing the number of CD16+ (FcyRIII) cells among activated Mc (Mph). At the same time, IL-8 detectably increased the number of cells expressing CD1 1 9 (receptor to interferon-y) and CD197 (CCR7), reducing the number of cells carrying CD124 (receptor to IL-4). In addition, IL-8 was able to enhance the secretion of IL-6 and IL-1 ß by activated Mph cells, without significantly affecting the production of TNF-а and IL-10. The data obtained indicate the ability of IL-8 to directly favor the pro-inflammatory activity of Mph cells.
Genes & Cells. 2018;13(1):65-69
pages 65-69 views

Expression of CD117 receptor in male gonads in traumatic brain injury

Fedotov A.V., Astrakhantsev A.F., Mazurova M.P.


Using the conventional histological methods (staining with hematoxylin and eosin), morphometric (counting the percentage of tubules with impaired spermatogenesis, measuring the crosssectional area of the tubules), as well as immunohistochemical methods of investigation (immunohistochemical staining with antibodies to C-kit (CD117), the gonads of 5 patients, who died from a craniocerebral trauma on the 15-35 day after the injury, and 6 patients who died from a craniocerebral injury at the scene. In both groups, a positive membranous staining of the spermatogonia of the basal section of the epithelio-spermatogenic layer is found, which is more pronounced in individuals who died in the long-term after traumatic brain injury, which may indicate activation of the proliferative activity of the spermatogonial population of regenerative nature. CD117 positive cell, similar to Cajal cells, are also detected in the walls of convoluted seminiferous tubules, located along the periphery of blood vessels, among interstitial endocrinocytes. The number of interstitial endocrinocytes, along with this, increases in the feces of the sex glands of individuals who died in the long-term after the craniocerebral trauma, which indicates their hyperplasia, as a compensatory adaptive response in response to atrophic changes in the epithelio-spermatogenic layer (so-called. "mixed atrophy of the testis”). CD117 positive cells, interacting with smooth muscle cells of the wall of convoluted seminiferous tubules, can participate both in the movement of spermatogenic cells from the basal membrane to the lumen of the tubule, and participate in the formation of the so-called. "Waves of spermatogenesis”, ensuring the movement of spermatogenic cells from the periphery to the middle zone.
Genes & Cells. 2018;13(1):70-74
pages 70-74 views

Intramiocardial administration of resident c-kit+ cardiac progenital cells activates epicardial progenitor cells and promotes myocardial vascularation after the infarction

Dergilev K.V., Tsokolaeva Z.I., Beloglazova I.B., Zubkova E.S., Boldyreva M.A., Ratner E.I., Diykanov D.T., Menshikov M.U., Parfenova E.V.


Resident cardiac progenitor cells reside in the adult heart and govern myocardial homeostasis and repair after injury. Many experimental and clinical studies are being completed with encouraging results. However, the mechanisms of the therapeutic action of CPC remain poorly understood. Initially they were explained by the ability of CPC to differentiate into cardiomyocytes and vascular cells, recently their regenerative effects are mainly explained by secretion biologically active molecules and the release of exosomes, which promote activation of the regenerative program in the heart cells. The aim of the present study is to assess the effect of intramyocardial CPC transplantation on the activation of the vasculogenic pool of epicardial cells. In our study we ligated the anterior descending coronary artery in the hearts of male Wistar rats and intramyocardial injections of a fluorescently labeled (CM-DIL+) CPC or control medium were performed. Fourteen days after transplantation, CPC retained viability, proliferation properties and some cells showed signs of vasculogenic differentiation. We did not find significant differences in the infarct size between two groups assessed by morphometric studies. However, CPC transplantation attenuated adverse remodeling: we found reduction in left ventricular dilatation, severity of transmural injury and activation of arteriogenesis in the border zone. By immunofluorescence staining of myocardial sections, obtained after CPC transplantation, we found a significant increase the number of Wt1+ cells in the epicardium, indicating activation of the epithelial-mesenchymal transition and the formation of epicardial progenitor cells (EPC). EPC migrated to the myocardium, some of them coexpressed markers CD31 (Pecam), alpha-smooth muscle actin (a-SMA), and participated in the new vessels formation. Thus, intramyocardial CPC transplantation increased the vascularization of the myocardium by differentiation of the transplanted cells, as well as the activation of vasculogenic epicardial cells, which can contribute the reduction of negative cardiac remodeling.
Genes & Cells. 2018;13(1):75-81
pages 75-81 views

Understanding mechanisms of the umbilical cord-derived multipotent mesenchymal stromal cell-mediated recovery enhancement in rat model of limb ischemia

Arutyunyan I.V., Fatkhudinov T., Elchaninov A.V., Makarov A.V., Vasyukova O., Usman N.Y., Marey M.V., Volodina M.A., Kananykhina E.Y., Lokhonina A.V., Bolshakova G.B., Goldshtein D.V., Sukhikh G.T.


Umbilical cord-derived multipotent mesenchymal stromal cells (UC-MMSCs) are considered as a strong candidate for cell therapy of lower limb ischemia. Sustained calf muscle ischemia with aseptic inflammatory response was induced in Sprague-Dawley rats by excision of femoral and popliteal arteries. uC-MSCs were injected into the calf muscle on day 7 after surgery. The animals were sacrificed on days 3, 10, and 30 after transplantation. Animals responded to the transplantation by temporary improvement in their locomotor function as assessed by the rota-rod performance test. Measured size of the lesions was significantly smaller in the experimental group than in the control group at all time points throughout the observation. The transplantation stimulated angiogenic processes on day 10 after transplantation. Living transplanted cells were traced for up to 30 days after transplantation, during which time they migrated to the damaged area to be partially eliminated by host macrophages; none of them differentiated into endothelial or smooth muscle cells of blood vessels. Additionally, the transplantation led to the predominance of activated pro-angiogenic and anti-inflammatory M2 macrophages by inhibiting the CD68+ macrophage infiltration and stimulating the CD206+ macrophage activation at the site of injury. A single intramuscular injection of allogeneic umbilical cord-derived mesenchymal stromal cells reproducibly facilitated recovery of structural and functional properties of surgically ischemized calf muscles in a rat. No differentiation of the transplanted cells in vivo was observed. The transplantation negatively regulated inflammation and enhanced tissue repair chiefly by modulating local patterns of macrophage activation.
Genes & Cells. 2018;13(1):82-89
pages 82-89 views

Combined use of plasmid drug pCMV-VEGFA and autodermoplasty for stimulation of skin defects healing in the experiment

Bilialov A.I., Abyzova M.S., Titova A.A., Mavlikeev M.O., Krilov A., Bozo I.Y., Deev R.V.


To find effective ways to stimulate chronic skin wounds healing (including deep burns, diabetic and trophic ulcers) is an actual multidisciplinary task. The aim of our study was to assess the potential of using autodermoplasty in combination with plasmid drug pCMV-VEGFA to optimize skin defects repair in the experiment. Autodermoplasty was performed on Wistar rats. The size of the skin flap was 2x2 cm. Immediately after surgery the animals of the test group (n=8) underwent intradermal injection in the periphery of autotransplant with 1 ml solution containing 0.3 mg of supercoiled plasmid DNA pCMV-VEGFA, rats of the control group (n=8) received 1 ml of 0.9 % NaCl. The results were analyzed in 3, 6, 9 12, 18 days using macroscopic evaluation, laser Doppler flowmetry, histological methods. Macroscopically in the test group necrosis of the transplanted skin flap was found at later periods of observation, in one case complete survival of autotransplant was observed. The results of laser Doppler flowmetry in the group with plasmid DNA did not have statistically significant differences with control. The wound defect diameter in the test group at 12 days was 5,52± 4.80 mm, in the control - 12,45±0,82 mm (p=0,03); 2,53±of 2,94 mm and 4,23±3,5 mm (p=0,067) at 18 days, respectively. At 18 days, the average number of vessels under the flap in the central zone were: of 26±2,9 in the test group and 20±8 - in control; it the peripheral zone - 27±3,4 and of 12,1±3,9 (p=0,035), respectively; in the skin muscle - 21,2±of 3,9 and 12,4±3,6 (p=0,04), respectively. Thus, the use of plasmid drug pCMV-VEGFA improved the skin healing after autodermoplasty.
Genes & Cells. 2018;13(1):90-94
pages 90-94 views

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