Vol 2, No 3 (2007)


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Historical articles

The centenary of cell biology: lessons for the future

Repin V.S.


Summing up the main events, discoveries and scientists within the «Cell Biology XX», the following topics are highlighted: 1) The beginning of cell biology and the epoch of vitalism - the impact of J. Loeb, R. Harrison, A. Carrel, T. Morgan and D.H. Wilson; 2) from cell ultrastructure to the concept of cell compartmentalization; 3) the beginning of systemic system biology and bioinformatics; 4) recombinant molecular cell biology; 5) developmental cell biology; 6) cell behavior in vitro and in situ; 7) organ and cell transplantation - the impact into basic cell biology; 8) post-genomic gigabyte cell biology: hurdles and limits for the next round of progress; 9) from molecular biology to modular biology; 10) the leading role of a new mega - international project in the XXI century.

Genes & Cells. 2007;2(3):9-17
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Cell technology

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Gene and stem-cell therapy for neurodegenerative diseases

Islamov R.R., Rizvanov А.А., Guseva D.S., Kiasov A.P.


Currently there are no available effective therapies for treating neurodegenerative diseases. In animal models, the loss of neurons, caused by mutations in known genes, can be alleviated by genetically modifying target cells to increase their regeneration and viability, or by replacing dead neurons with new healthy neural cells by neurotransplantation of stem or progenitor cells, differentiated in neural pathway. Here we summarized results for gene therapy using antisense oligonucleotides, siRNA, and viral vectors. Critically reviewed advantages and disadvantages of neurotransplantation of embryonic and different adult stem cells. To date we found no reports of using genetically modified stem cells from umbilical cord blood for cell therapy of neurodegenerative diseases. We state a hypothesis, that stem cells from umbilical cord blood, genetically modified by transfection with plasmid vector, simultaneously expressing neural cell adhesion molecule L1 and vascular endothelial growth factor [VEGF), could have a significantly enhanced therapeutic effect in transgenic mice G93A, which serve as animal model for amyotrophic lateral sclerosis [ALS).

Genes & Cells. 2007;2(3):29-37
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Cell technologies in the treatmemt of critical lower limbs ischemia

Smolyaninov A.B., Pykhtin E.V., Bulgin D.V., Tomonaga M.


This article presents reviews application of cell technologies in the treatment of critical limb ischemia. Surgery treatment remains a basic method in the treatment of vascular obliterans limb diseases. In our days surgical methods are known as the most effective treatment of main artery atherosclerosis, but this kind of treatment is not so good for treatment peripheral arterial diseases such as thromboangitis obliterans (Buerger’s disease) because of often restenosis and rethrombosis development. Principal purpose efforts of surgeons according on ensuring of adequate blood flow in terminal parts of limb and also on support effective perfusion of tissue. This aim could be obtain due to undirected revascularization. Recently thanks to development of cells technologies on a level with osteothrepanation and lumbal sympathectomy it became possible to create new ways of roundabout blood flow in ischemic limb. Autological stem cells transplantation to patients with critical ischemic limb provides an appearance of new sites revascularization. In last years experimental and clinical studies in this area confirm safety and efficiency of the stem cells transplantation to patients with ischemic limb disease. However, few questions about quality and quantity of stem cells which are necessary for appearance revascularization remain unknown.

Genes & Cells. 2007;2(3):40-46
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Original Study Articles

Continuity of cytogenetic characteristics in passages of mice embryonic germ cell line G1

Glazko T.T., Yacishina A.P., Pidpala O.V., Lukash L.L.


The comparative analysis of cytogenetic characteristics in populations of cells of different passages of mice embryonic germ cell line G1 received from sexual puff of 12,5 days of embryo of the mouse of line BALB/c was carried out. It was revealed, that despite of the expressed heterogeneity of cells on number of chromosomes, Robertsonian translocation, some line specific karyotype features were characteristic for all investigated cell populations. It was, in particular, the closest of the chromosome numbers to penta- and hexaploidies, and also the presence of translocation t(6;12). The possible connections between revealing karyotype traits and the mechanisms of maintenance of cell polypotency and proliferation in cultural condition were discussed.

Genes & Cells. 2007;2(3):47-50
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CXCR4 expression and CD34+ hematopoietic stem cells mobilization efficacy

Kurtova A.V., Estrina M.A., Alexeev S.M., Trofimova S.A., Tupitzina O.A., Karpov V.G., Zdorov A.E., Afanasiev B.V., Zueva Y.E.


CXCR4 is a chemokine receptor which is essential for targeted migration of hematopoietic stem cells (HSC). CXCR4 is known to be an indirect target for G-CSF stimulation. The aim of this study was to evaluate the level ofCXCR4 expression on the surface of HSC, collected from apheresis products of patients with different responses to G- CSF-stimulation. Cord blood, normal bone marrow and primed bone marrow samples were analyzed to be compared with apheresis product. It was demonstrated that mean fluorescence intensity of CXCR4 indicating the density of CXCR4 expression on HSC surface is diminished after G-CSF stimulation towards normal bone marrow ? primed bone marrow ? apheresis product from mobilizable patients and demonstrates negative correlation with mobilization efficacy. CXCR4 expression on the surface of HSC from non-mobilizable patients does not differ from other native sources, such as normal bone marrow and cord blood, that points out the intrinsic unresponsiveness to G- CSF treatment or other kinetics of mobilization in poor-mobilizable patients.

Genes & Cells. 2007;2(3):51-56
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Immunoregulative properties of human fetal hepatic stem cells

Petrenko Y.A.


Human fetal liver is unique as it contains stem hematopoietic cells and their committed derivatives of different maturation. The present study was aimed to assess the amount of immunocompetent human fetal hepatic cells of 9-10 week gestation by phenotypic properties and their reaction to mitogens as well as to evaluate influence of human fetal hepatic cells to proliferation of peripheral blood lymphocytes of adult donors in a mixed culture.

The suspension of human fetal hepatic cells was obtained by a mechanical method using vibration. Cells were cryoconserved under the protection of 5% DMSO at the speed of 1 °С per min. Fluorescent microscopy was used for immune marker analysis. The proliferation activity of fetal hepatic cells and adult peripheral blood lymphocytes was assessed according to 3H-thymidine inclusion. In the mixed culture human fetal hepatic cells were co-cultured with peripheral blood lymphocytes in the presence or absence of mitogens.

Immune marker analysis of the fetal hepatic cells suspension did not reveal the statistically relevant number of matured B- and T- lymphocytes. Unlike adult peripheral blood lymphocytes human hepatic cells demonstrated high levels of spontaneous proliferation when cultured in vitro. Mitogens, phytohemagglutinine (PHA) or concanavalin А (Con-А) suppressed the proliferation of human fetal hepatic cells. In the mixed culture the fetal hepatic cells suppressed both spontaneous and mitogen-stimulated proliferation of adult peripheral blood lymphocytes as well as peripheral lymphocyte proliferation in a twoforked mixed culture. Possible mechanisms of fetal hepatic cells activity have been discussed in the article.

Genes & Cells. 2007;2(3):57-61
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Characteristics of bone marrow stromal cells in mixed lymphocytes culture response

Griegoryan A.S., Tsypkina N.V., Sergeev V.S., Deev R.V., Pinaev G.P.


At present more and more attention has been given to stromal cells of bone marrow (BMSCs) due to the possibility of using them as immunomodulators in clinical practice. Some investigators have noticed suppressive effect of bone marrow stromal cells on lymphocytes proliferation in mixed cultures. Properties of allogenous and syngeneic BMSCs in vitro have been studied. BMSCs influence on lymphocytes proliferation was assessed by the lymphocytes mixed culture response, the results were visualized with immune cytochemic staining of cells in S-phase on Bromdesoxiuridin (BrdU) inclusion. Bone marrow stromal cells, spleenocytes, and fibroblasts were obtained from Wistar rats and outbred rats. Both allogenic and syngeneic bone marrow stromal cells have not been shown to suppress lymphocytes proliferation. Moreover, allogenous BMSCs stimulate lymphocytes proliferation both in lymphocytes mixed culture response and in co-culturing. At the same time, proliferation of lymphocytes in response to allogenous BMSCs reaches 85% in BMSCs high concentrations, that is relevantly more than proliferation of lymphocytes in response to allogenous fibroblasts. It has been stated that supernatants of BMSCs cultures produce proliferation of lymphocytes as well.

Genes & Cells. 2007;2(3):62-66
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Clinical experience

Transplantation of autologous mesenchymal stem cells on demineralized bone matrix in treatment of pseudoarthrosis of long bones

Shchepkina E.A., Kruglyakov P.V., Solomin L.N., Zaritsky A.Y., Nazarov V.A., Viyde S.V., Shvedova E.V., Tykhilov R.M., Polyntsev D.G.


The article deals with the results of clinical trial-1 of a treatment modality of pseudoarthrosis (priority on the 23rd May, 2006, file number 2006117605) using biotransplant that is demineralized bone allotransplant colonized by autologous mesenchymal stromal cells with the density of 7-10x106 in 1cm2. Pseudoarthrosis of femoral bones and tibia was treated in 9 patients, with transosseous osteosynthesis being used in every case. In uncomplicated postoperative period the apparatus was dismantled and support ability of the leg was restored in 3 to 5 months, that is comparable to the time of healing of fractures of the same location. According to the X-ray and CT data the transplant density increased progressively without preliminary resorbtion, consolidation occurred mainly via transplant that allows to suppose not only osteoinductive influence, but also osteoconductive role.

Genes & Cells. 2007;2(3):67-74
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Stem Cells Business

Hematopoietic progenitors mobilization market: Is there time to change?

Kurtova A.V.


The purpose of this review is to perform a comprehensive comparative analysis of different hematopoietic progenitor’s mobilizers with short excursus to mobilizers’ market development. Special attention is paid to the new drugs with great clinical perspectives.

Genes & Cells. 2007;2(3):75-78
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5th ISSCR Annual Meeting

Kiselev S.L., Lagarkova M.A.
Genes & Cells. 2007;2(3):79-80
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