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Vol 6, No 2 (2011)


Interview with professor Alejandro Madrigaland professor Manuel Fernandez

Deev R.V., Stepanov Е.V.


- Dear gentlemen, first of all, let me thank you for finding time to visit our symposium. We conduct such events on an annual basis, but this is the first time it covers issues in the field of hematology. You are well-known top specialists. Why did you agree to participate and give lectures.
Genes & Cells. 2011;6(2):6-9
pages 6-9 views

Clinical importance of maternal microchimerism in children

Rumyantsev A.G., Kurtser M.A., Mareeva Y.B., Misyurin A.V., Rumyantsev S.A., Ustyugov A.Y.


Bilateral exchange with blood cells and cell-free substances between a mother and a fetus and visa verse routinely occurs during normal pregnancy. A term of microchimerism (MC) implies a few number of cells (or DNA) detected in a child and/ or a mother which primarily originated in a genetically different individual. Whereas MC might result from iatrogenic exposure on an organism such as transplantation or transfusion, the main source of MC is a naturally acquired condition as a result of transplacental interactions between a mother and a fetus during pregnancy. The present interest to MC can be explained by many reasons. During pregnancy fetal cells can be found in a mothers blood in prenatal diagnostics. Moreover, investigation of fetal MC might elucidate some complications due to pregnancy such as preeclampsia, or give a new insight into pathogenesis of autoimmune diseases such as rheumatoid arthritis, whose clinical manifestation subsides during pregnancy. Furthermore, it is known at present that MC retains for a long time after a child delivery where it occurs both with fetal MC acquired by the woman during pregnancy and with maternal MC in her descendants. Investigations of long-term effects of fetal and maternal MC is a novel, active research, its results indicate both favourable and unfavourable long-term effects of MC. The present article is a review of available data on maternal or, to be more precise, maternal-fetal microchimerism and described or experimentally proposed its consequences.
Genes & Cells. 2011;6(2):10-14
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Derma fibroblasts: peculiarities of cytogenesis, histophysiology and possible clinical use

Zorina A.I., Bozo I.Y., Zorin V.L., Cherkasov V.R., Deev R.V.


Gaining current experimental data a major concept on fibroblasts, the main cells of loose and dense connective tissue, undergoes significant changes moving away off classical concepts. Considering fibroblasts as a true phenotypic category we tried to address most challenging issues relating to definition of a fibroblast differon, cellular sources of their cytogenesis, histophysiology, their ageing changes in terms of influence on possible clinical use.
Genes & Cells. 2011;6(2):15-26
pages 15-26 views

Mechanisms of immunomodulatory effects of mesenchymal stem cells

Ivanyuk, D.I., Turchin, V.V., Popandonulo, A.G., Grin V.K.


Mesenchymal stem cells play different roles in organism and are capable to differentiate into mesenchymal cells line (osteoblasts, chondrocytes, adipocytes) and other cell lines. MSCs also can interact (directly and indirectly) with almost all cells of immune system via soluble factors and cell-contact interactions and substantially modulate immune response of an organism. MSCs can be applied in medical practice as the safe immunosuppressive agent for allogenic transplantation and for treatment of autoimmune diseases. This review deals with interactions between MSCs and immune cells and mechanisms of MSC-induced immunosuppression.
Genes & Cells. 2011;6(2):27-31
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Induced pluripotent stem cells as a model for studying human diseases

Nekrasov E.D., Lagarkova M.A., Kiselev S.L.


Induced pluripotent stem cells are able for infinite selfrenewal and differentiation into all types of cells. The review is focused on modern methods and approaches to create models of human diseases based on human induced pluripotent stem cells, recent advances and prospects in this area, as well as the application of such models to study human diseases.
Genes & Cells. 2011;6(2):32-37
pages 32-37 views

Personalized cell therapy in ophthalmology. I. Method for obtaining and phenotype of autologous product

Avetisov S.E., Subbot A.M., Antochin A.I., Kasparova E.A., Kasparov A.A., Pavliuk A.S.


The method for obtaining activated in vitro by poly A:U autologous leucocytes from peripheral blood for corneal diseases treatment is developed. Method allows us to obtain a product with sufficient content of viable nucleated cells (up to 3106 cell/ml). Cellular composition of the product was determined. Mononuclear fraction decreased in 1,3 times and granulocyte portion is increased. Phenotype of lymphocytes in the cell product is the same as in peripheral blood, with selective loss of B-lymphocytes. The presence of CD14+/34low cells, which are considered to be progenitors, is defined in the product. Using of cell product, obtained by designed technique, may be promising in clinic, because of it minimal traumatism for the patient and simplicity.
Genes & Cells. 2011;6(2):38-42
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Dynamics of a growth factors serum level in therapy of myocardial infarction with mesenchymalstem cells in an experiment

Golovkin A.S., Velikanova E.A., Matveeva V.G., Saveleva E.A., Eremeev A.V., Sheina Y.I., Svetlakov A.V.


The aim of the work was to assess TGF в, VEGF-C and GM-CSF concentrations in the serum of rats after postinfarct intramyocardial injection of mesenchymal stem cells. Myocardial infarction was simulated by the criodestruction of the left ventricular anterior wall. Mesenchymal stem cells were derived from rat bone marrow and injected into myocardium 21 days after the crioinjury. The levels of TGF в, VEGF-C and GM-CSF were measured at 3, 7 and 14 days. The synthetic activity of the transplanted cells to these growth factors in vitro was also measured. It was shown that the administration of mesenchymal cells leads to an increased level of TGF в in the peripheral blood. The maximum TGF в concentration was observed on Day 7 after transplantation. Despite the intensive synthesis of VEGF-C and GM-CSF by mesenchymal cells in vitro, they do not demonstrate a significant effect on the level of the studied growth factors in the peripheral blood.
Genes & Cells. 2011;6(2):43-47
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Systems approach to the guarantee of quality of mesenchymal stem cells of bone marrow for the clinical use

Shachpazyan I.A., Kobzeva I.V., Astrelina T.A., Yakovleva M.V., Osipova E.Y., Skorobogatova E.V.


Mesenchymal stromal/stem cells (MSCs) of bone marrow (BM) origin not only provide the supportive microenvironmental niche for hematopoietic stem cells (HSCs) but are also capable of differentiating into various cell types of mesenchymal origin, such as bone, fat, and cartilage. The role is known for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus host disease (GVHD) during allogeneic transplantation. Purpose: to estimate quality and biological safety the MSC of bone marrow for the transplantation. Were analyzed data expansion MSC of 94 BM at the Stem Cell Bank of Moscow between 2007 and 2010 on the registered medical technologies. MSC were revealed in the native form or frozen in liquid nitrogen. Quality, MSC was evaluated with of the bacteriological and virusological control; determined the viability of cells with the trypan blue and 7AAD; markers that specifically identifies MSCs: CD73+; CD 90+; CD105+; CD45-; CD34-; CD14; CD133-; CD19-; HLA DR- by flow cytometry. The biological safety (karyotype) was analyzed by G-banding technique; 15-30 metaphase cells for each culture were analyzed. To analyze the level aneuploidy, fluorescent in situ hybridization (FISH) with chromosome enumeration probes (CEP) studies was performed. Are developed the documents, which regulate the stages of the work of expansion MSC of BM. Were prepared 71 MSC of BM (157 doses) and were used for allogeneic transplantation 23 to patients (70 doses MSC) for the purpose of adherence HSC, reducing the incidence and severity of GVHD. In the majority of the cases of transplantation MSC it was carried out at the dose of 2 ×106/kg. There were no acute reactions during the transplantation MSC BM. Thus, the estimation of quality and safety MSC of BM for allogeneic transplantation, included: a conducting of documentation on GMP to standards, inspection of a quantity of cells for achievement of optimum dose, bacteriological and virusological control, confirmation the markers that specifically identifies MSCs and the estimation of biological safety.
Genes & Cells. 2011;6(2):51-54
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«Niche - relief» conception for stem cells as a basis of biomimetic approach to boneand hemopoietic tissues engineering

Khlusov I.A., Shevtsova N.M., Khlusova M.Y., Zaitsev K.V., Sharkeev Y.P., Pichugin V.F., Legostaeva E.V.


An affect of relief features and quantitative parameters of model mineral matrix on in vitro structure-functional status of human lung prenatal stromal cells (HLPSC) and in vivo remodeling of mice bone/marrow system has been studied. According to data established, rough (Ra > 2 m) implants with calcium phosphate micro-arc coatings simulate three-dimensional state of regenerating bone matrix. Such surfaces have own structure-functional sites (microregions) which were named by niche - relief and were necessary for maturation and differentiation of HLPSC to secreting osteoblasts. Maximum remodeling of mice bone/marrow system in heterotopic test in vivo was also observed under optimal parameters of osteogenic niche in vitro (approximately 43% average index of cellular alkaline phosphatase square to artificial microregion area). A probable cell-molecular mechanism of influence experimental 3D-modeling of bone surface on selection of quiescent or active state by endosteal niche has been detected. It connects with activating cellular production of bone matrix components (alkaline phosphatase, osteocalcin, collagen, calcium phosphates) that dissociate dimensionally stromal and hemopoietic elements, and with parallel diminishing TNF secretion in intercellular medium. The data obtained develop our previous speculations about existence and sizes of artificial endosteal niche for osteogenic differentiation of multipotent mesenchimal stromal cells.
Genes & Cells. 2011;6(2):55-64
pages 55-64 views

Effects of Н2О2-plasma processing on properties of cellular scaffolds made of «Bioplastotan»resorbing polyesters

Nikolaeva E.D., Goncharov D.B., Shishatskaya E.I.


Produced from «Bioplastotan» resorbing polyesters (linear polyesters of hydroxyl derivatives alkanoic acids) scaffolds for cell culturing such as films, pressed 3-D forms and nonwoven fabric from ultrathin fibers are characterized. Two types of polymers - a homopolymer of the 3-hydroxybutyric acid and a copolymer formed by monomers of the 3-hydroxybutyric and 3-hydroxyvalerianic acids are studied. Surface properties of developed polymer scaffolds, sterilized with autoclaving and Н2О2-plasma processing are compared. It is shown that plasma has beneficial effects resulting in decrease of the watering contact angle and increase of surface hydrophilic properties. Positive effects of Н2О2-plasma processing of scaffold surface on culturing cell adhesion and viability compared with autoclaving sterilization is demonstrated on NIH 3T3 line fibroblast culturing.
Genes & Cells. 2011;6(2):65-70
pages 65-70 views

Tsirkuliruyushchie gemopoeticheskie i endotelial'nyepredshestvenniki v perifericheskoy krovi patsientovs cherepno-mozgovoy travmoy

Chernykh V.A., Pronkina N.V., Stupak V.V., Fonin V.V., Shishlov P.E., Shevela E.Y., Leplina O.Y., Chernykh E.R., Ostanin A.A.


В настоящей работе исследована мобилизация ге- мопоэтических стволовых/прогениторных клеток (ГСК) и эндотелиальных предшественников (ЭП) у больных с черепно-мозговой травмой (ЧМТ). В первые 24-48 ч по- сле ЧМТ выявлено достоверное возрастание абсолютного количества циркулирующих CD34+CD45+ГСК, а также от- носительного и абсолютного количества CD34+CD144+ЭП. Эффективность мобилизации ГСК была достоверно выше в группе больных до 40 лет, и относительное содержание CD45+CD34+ клеток находилось в обратной зависимости от возраста пациентов (r = -0,54, р = 0,039). Возрас- тание CD45+CD34+ГСК и CD34+CD144+ЭП регистриро- валось как у больных с легкой, так и среднетяжелой/тя- желой ЧМТ и не зависело от уровня сознания по шкале комы Глазго (ШКГ). Однако у больных с отсутствием воз- растания CD45+CD34+ клеток частота неблагоприятных исходов (1-3 балла по шкале исходов Глазго; ШИГ) была достоверно выше, чем в подгруппе больных с повышенным количеством ГСК (p = 0,047). Выявлена также значимая взаимосвязь ранних ЭП, не экспрессирующих VE-кадгерин (CD3-CD34+CD144-ЭП), с тяжестью/исходом ЧМТ (r = 0,6; p = 0,017 и r = 0,53; p = 0,035, соответственно). Таким образом, интенсивность мобилизации ГСК и ЭП у больных ЧМТ может быть использована в качестве прогностического фактора, свидетельствующего о репаративном потенциале костномозговых предшественников.
Genes & Cells. 2011;6(2):71-77
pages 71-77 views

Sinusoidal liver cells and bone marrow cells as components of the common functional systemfor regulation of recovery morphogenesis of healthy and damaged liver

Onischenko N.A., Lyundup A.V., Deev R.V., Shagidulin M.Y., Krasheninnikov M.E.


This review presents current information about the cooperative interaction of sinusoidal liver cells and bone marrow cells at the processes of physiological, reparative and fibrosing liver regeneration. It is shown that the stem / progenitor cells of bone marrow (hematopoietic and mesenchymal stromal cells) supplement regulatory role of liver stem cells (first of all stellate cells - Ito cells), reduce the seriousness of inflammation and fibrosis, and thereby normalize the recovery process of damaged liver regeneration. It is believed that the use of mesenchymal stromal cells of bone marrow is the most future forward strategy. However, to form a final opinion on the regenerative capacity of autologous and allogeneic bone marrow cells at hepatic failure large-scale double-blind clinical trials should be carried out.
Genes & Cells. 2011;6(2):78-92
pages 78-92 views

A concept of cytoregulation therapy in brain glial tumors: novel theoretical and methodological platformof using cell-based technologies in neuro-oncology

Bryukhovetsky A.S., Bryukhovetsky I.S.


Current standard methods of curing patients with brain tumors targeted to complete elimination of tumor cells from the body are of low effectiveness. Disappointing results of generally accepted therapy modalities ordain searching for novel approaches to treatment with oncopathology, based on detailed understanding of oncogenesis and interaction of tumor cells with the body normal ones. In this discussion article on the basis of the developed hypothesis of induced bioregulation of tumor cells we have proposed a conceptually different methodological concept of therapeutic correction brain tumors - cytoregulatory therapy which is based on using induced regional multipotent stem cells as the main approach in the central nervous system tumors.
Genes & Cells. 2011;6(2):93-103
pages 93-103 views

Influence of Autologous Connective Tissue (Stromal) Bone Marrow Cells (SBMC)Upon Delayed-Forming Distraction Regenerates in Children

Mironov, S.P., Omelyanenko, N.P., Kzhevnikova O.V., Ilina, V.K., Ivanov, A.V., Karpov I.N.


Results of cultivated autologous connective tissue bone marrow cells use for the stimulation of distraction bone regenerates in 8 children aged from 3.7 to 16.0 years with congenital lower extremities length discrepancy (main group) are compared with those achieved for 24 children aged 2.5-14.0 with similar pathology who were treated without application of cell technology (control group). Treatment results are indicative of marked stimulating effect of cell therapy upon the formation and maturation of distraction bone regenerates after surgical correction of lower extremities length discrepancy. In the main group duration of treatment reduced to 4,5-6,5 months versus 7,5-11 months in the control group. Subsequently with growth of children the elongated limb segments in children from the main group showed less delay in development as compared with elongated limb segments in patients from the control group. It is obvious that use of SBMC has exerted stimulating effect upon the growth of the whole segment of the operated extremity approximating the rates of its development the physiological ones. Reduction of treatment duration enabled to avoid potential complications related to prolonged extremity fixation in distraction apparatus and to perform rehabilitation at earlier terms than in patients from the control group that led to the improvement of anatomical and functional results.
Genes & Cells. 2011;6(2):104-112
pages 104-112 views

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