Vol 11, No 4 (2016)

Full Issue


Plant and animal stem cells: two sides of the same medal

Zubov D.A.


The review offers up-to-date analysis on plant stem cell biology, meristems functioning, including plant regeneration mechanisms and tumorigenesis, as well as biotechnology methods of plant tissue culture. There were also compared the plant and animal stem cells, their probable polyphyletic origin in aspect of divergent evolution of modular and unitary organisms in both plant and animal kingdoms.
Genes & Cells. 2016;11(4):6-17
pages 6-17 views

Sepsis and apoptosis

Khaertynov K.S., Anokhin V.A., Boichuk S.V., Rizvanov A.A.


The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis.
Genes & Cells. 2016;11(4):18-21
pages 18-21 views

Cell therapy of osteogenesis imperfecta

Sergeev V.S., Tichonenko T.I., Buklaev D.S., Baindurashvili A.G., Afanasiev B.V.


Genetically determinated type I collagen structure anomaly causes the group of innate diseases known as osteogenesis imperfecta. Type I collagen is the basic component of the bone tissue organic matrix and is produced by osteoblasts. The replacement cell therapy can be a radical treatment option for the osteogenesis imperfecta if the high stable osteoblast chimerism level is reached. Analogously with the classical hematopoietic stem cell transplantation the replacement of hypothetic osteogenic stem cells is necessary for the stable osteoblasts engraftment. Stem cells with the potency to skeletal tissues differentiation were first described by A.J. Friedenstein in the bone marrow stroma. The evolution of the stromal stem cells vision leaded to the “mesenchymal stem cells”, “stem cells of skeletal tissues” and even “medical signal cells” concepts appearance. The transplantation of all listed cell types can lead to the increase of the clinical status in patients with osteogenesis imperfecta which is temporary yet. There was no success in the achievement of the stable osteoblasts engraftment during experimental and clinical studies at the moment. Such fact could be associated with the deficiency of fundamental knowledge about the source osteoblasts origin in vivo. At the same time taking into account extremely low range and poor efficiency of current severe osteogenesis imperfecta forms therapy approaches the cell therapy with ex vivo cultivated bone marrow stromal cells application is quite promising.
Genes & Cells. 2016;11(4):22-33
pages 22-33 views

Biological activity comparative evaluation of the gene-activated bone substitutes made of octacalcium PHOSPHATE AND PLASMID DNA CARRYING VEGF AND SDF GENES: PART 1 - IN VITRO

Bozo I.Y., Maiorova K.S., Drobyshev A.Y., Rozhkov S.I., Volozhin G.A., Eremin I.I., Komlev V.S., Smirnov I.V., Rizvanov A.A., Isaev A.A., Popov V.K., Deev R.V.


High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor-1а (SDF-1a). The aim of the study was to evaluate the cytotoxicity of the gene-activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo. свойств и обладали специфической активностью в виде увеличения экспрессии терапевтических генов. Однако дальнейшие исследования необходимы для детализации выявленных особенностей и оценки реализуемости биологического действия in vivo.
Genes & Cells. 2016;11(4):34-42
pages 34-42 views

Osteogenic potential of multipotent mesenchymal stromal cells from human exfoliated deciduous teeth before and after cryopreservation

Bukharova T.B., Leonov G.E., Galitsyna E.V., Vasilyev A.V., Vakhrushev I.V., Vikhrova E.B., Makhnach O.V., Goldstein D.V.


The use of multipotent mesenchymal stromal cellsfrom human exfoliated deciduous teeth (SHED) to stimulate bone regeneration requires data on the influence of cryopreservation on the osteogenic differentiation capacity of these cells. SHED were subjected to cryopreservation. Before freezing and after thawing, cell cultures were exposed osteogenic differentiation with vitamin D3 or dexametasone and assessed for expression of the osteogenic markers osteocalcin, alkaline phosphatase, BMP-2 and RunX2 using real-time qPCR. Extracellular matrix (ECM) mineralization was evaluated by Alizarin red staining. Supplementation of osteogenic medium with vitamin D3 increased the expression of the osteogenic markers osteocalcin, alkaline phosphatase, BMP-2 and RunX2 as well as promoted an increase in the synthesis and mineralization of ECM in the cells both before and after cryopreservation. In the presence of vitamin D3 gene expression of alkaline phosphatase, BMP-2 and RunX2 after cryopreservation was higher than before freezing. Gene expression of osteocalcin, BMP2 RunX2 in osteogenic medium with vitamin D3was higher compared with dexamethasone for 14 days differentiation both before or after cryopreservation. The maintenance of SHED osteogenic differentiation potential after long-term cryopreservation provides a basis for banking of these cellsfor further auto- or allotransplantation.
Genes & Cells. 2016;11(4):43-47
pages 43-47 views

Development of tissue-engineered chitosan-polycaprolactone blends for vascular surgery

Zakharova I.S., Smirnova A.M., Zhiven' M.K., Saaya S.B., Shevchenko A.I., Zakian S.M., Ivanova L.N.


Tissue engineering provides the opportunity to minimize some possible negative results of the synthetic vascular grafts in long-term follow-up. The choice of the optimal scaffold and cell source for seeding are key conditions to bring properties of vessel substitute to physiological. In some works it is shown that a chitosan-polycaprolactone blend is a suitable biodegradable material for tissue engineering. In this paper we suggest an efficient method to generate of tissue-engineered chitosan-polycaprolactone blends, cellularized by endothelial cells of human cardiac explants. The cells cultured on the blended membranes retain their functional properties: viability and proliferative properties; maintain specific endothelial antigens and synthesis of extracellular matrix. These results suggested that tissue-engineered chitosan-polycaprolactone blends seeded by endothelial cells of human cardiac explants may be potential to development of substitutes for small diameter blood vessels.
Genes & Cells. 2016;11(4):50-56
pages 50-56 views

Fascaplysinis a promising agent for the creation of new treatments' methods of glial brain tumors

Bryukhovetskiy I.S., Zhidkov M.E., Kudryavtsev I.V., Polevshikov A.V., Mishchenko P.V., Milkina E.V., Bryukhovetskiy A.S., Zaitsev S.V., Lyahova I.A., Vikhareva V.V., Khotimchenko Y.S.


The effectiveness of glial brain tumors treatment remains low. Standard treatments do not provide a radical removal of tumor cells infiltrating the brain substance. One solution to this problem is to find new compounds with high anti-tumor activity and the methods' development of targeted delivery. Our attention was drawn to a group of compounds, which are based on pentacyclic system of pyrido[1,2-a: 3,4-b'] diindols. The most famous representative is fascaplysin. It is the first substance isolated from a marine sponge Fascaplysynopsis sp. The objective was to explore the characteristics and mechanisms of the cytotoxic and cytostatic effect of fascaplysin on C6 glioma cells in vitro, and to compare the effectiveness fascaplysin and temozolomide in vitro and in a targeted delivery to the tumor in vivo. We used techniques: mammalian cell cultures, high-performance robotic quantitative microscopy, confocal laser fluorescence microscopy, flow cytometry, modeling of glioblastoma in vivo, pharmacological testing, magnetic resonance imaging. It is shown that fascaplysin induces apoptosis in C6 glioma cells. At a concentration of 2 uMfascaplysin was more effective than the temozolomide. Decrease of concentration below 0.5 uM resulted to reduction of cytotoxic effects. The severity of cytostatic effect increased with increasing exposure time. Targeted delivery the fascaplysin to the tumor using transport capacity of stem cells increased the lifespan of rats and decrease in tumor size.
Genes & Cells. 2016;11(4):57-69
pages 57-69 views

Multipotent stromal cells in the treatment of acute liver failure after extended hepatectomy in the experiment

Rudakov V.S., Voskanyan S.E., Eremin I.I., Onnitsev I.E., Deev R.V., Naydenov E.V., Eremin P.S., Y.A. Zhgutov 1.1.


Resection of the liver is the main method of treatment in primary and metastatic liver tumors. Frequent complication after extended hepatectomy is acute liver failure, which occurs in 33.83% of cases and may lead to death. The aim of this study is to determine the therapeutic potential of multipotent mesenchymal stromal cells in the treatment of acute liver failure after extended hepatectomy in animal models (rats). The liver mass (before and after 70% hepatectomy), synthetic function of the liver, the level of liver enzymes were measured. The results showed that transplantation of 2.5 mil. of multipotent mesenchymal stromal cells of bone marrow into the inferior vena cava improves liver function and decrease the level of liver enzymes. We observed better recovery of liver mass, and liver functional test (total protein, albumin, alkaline phosphatase, INR, APTT, direct bilirubin) in the experimental group. Thus, multipotent mesenchymal stromal cells have therapeutic effect in treatment of acute liver failure after extended hepatectomy in the experiment. However, more research is needed to understand the mechanisms of therapeutic action of these cells after extended hepatectomy.
Genes & Cells. 2016;11(4):70-74
pages 70-74 views

The dependence of proliferation rate of human dermal fibroblasts on growth medium composition and fetal bovine serum concentration

Fadeyev F.A., Lugovets D.V., Ulitko M.V., Leontyev S.L., Sazonov S.V.


Application of dermal fibroblasts for therapy requires the use of large volume of cell material. The automatized cultivation provides stable conditions for GMP-grade cell production. To define the effect of serum concentration on proliferation rate, fibroblasts were cultured in growth media with different serum percentage. The proliferation rate was evaluated by the use of average period of cell population doubling. For choosing the optimal culture medium, different types of media together with their mixtures, produced by Gibco and PanEco, were explored. It was shown that exponential decrease of the period of cell population doubling occurs when the serum concentration rises from zero to 1 2%, and further increment of serum percentage is followed only by minor reduction of this value. The highest proliferation rate of dermal fibroblasts is obtained when they are cultivated in aMEM medium or in the mixtures of aMEM with F-12, Advanced DMEM with F-12 and Advanced DMEM with RPMI-1640 media (Gibco, USA).
Genes & Cells. 2016;11(4):75-79
pages 75-79 views

Frequencies of the KITLG, BAK1 and SPRY4 alleles and genotypes associating with the development of testicular germ cell tumors, are increased in patients with testicular microlithiasis

Dantzev I.S., Ivkin E.V., Tryakin A.A., Bulanov A.A., Godlevski D.N., Latyshev O.Y., Rudenko V.V., Tyulyandin S.A., Volodko E.A., Okulov A.B., Loran O.B., Nemtsova M.V.


Testicular microlithiasis is a random finding on ultrasound testicular examination. Testicular microlithiasis is of particular interest as an informative marker in men with an increased risk of testicular germ cell tumors. Genes KITLG, SPRY4 and BAK1 influence the development of the testes and spermatogenesis, their change results in a significant increase in the risk of testicular germ cell tumors. To determine the genetic factors that determine an increased risk of testicular germ cell tumors in patients with testicular microlithiasis, we investigated the frequency of alleles and genotypes of genes KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876) and BAK1 (rs210138) in groups of fertile male, patients with testicular germ cell tumors and patients with testicular microlithiasis. For KITLG rs995030 we found significant differences in the frequency of the genotype GG in patients with testicular microlithiasis (p = 0.013) and in patients with testicular germ cell tumors (p = 0,0031) compared with the control. For KITLG rs1 508595 revealed significant differences in the frequency of G allele and GG genotype in patients with testicular microlithiasis (p = 0,002 for allele, p = 0,01 for genotype) and patients with testicular germ cell tumors (p = 0.0003 for allele; p = 0,014 for genotype). For BAK1 rs210138 we found significant differences in the frequency of G allele in patients with testicular microlithiasis, compared with the control group (p = 0,03). With a combination of high-risk genotypes study KITLG (rs995030, rs1508595) an BAK1 (rs210138) showed that the combination of these genotypes were significantly more common in patients with testicular germ cell tumors (p = 0,0001) and patients with testicular microlithiasis (p = 0,0053), on compared with the control. We have shown an increase in frequency of genotypes combination for testicular germ cell tumors at 4,6 times (OR: 4,669 [2,172-10,034]), and testicular microlithiasis - 3,3 times (OR: 3,355 [1,471-7,654]).
Genes & Cells. 2016;11(4):80-83
pages 80-83 views

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