Mechanisms of Stimulation of the Growth of Mouse Mammary Adenocarcinoma by Mesenchymal Stem Cells.

Mesenchymal stem cells from the adipose tissue (AT MSC) and the bone marrow (BM MSC) stimulated migration of melanoma B16 cells, while mammary adenocarcinoma Ca755 cells stimulated migration of mesenchymal stem cells. Mesenchymal stem cells retained these properties at late terms after γ-irradiation in vitro. Tumors that developed after injection of Ca755 cells alone and in combinations with BM MSC or AT MSC had similar histological structure corresponding to breast adenocarcinoma. Only AT MSC stimulated tumor growth, which was determined by more intensive secretion of factors stimulating proliferation of tumor cells, including chemokine CCL2. The use of AT MSC in regenerative medicine requires careful monitoring of the absence of tumors in patients.

Proliferative and Differentiation Potential of Multipotent Mesenchymal Stem Cells Cultured on Biocompatible Polymer Scaffolds with Various Physicochemical Characteristics.

Biocompatibility of film and fibrous scaffolds from polylactide-based polymers and the relationship between their architecture and the functional characteristics of mesenchymal stem cells were studied. Cell culturing on polylactide-based film and fibrous matrixes did not deteriorate cell morphology and their proliferation and differentiation capacities. The rate of cell proliferation and penetration in microporous 3D matrices with the same porosity parameters and pore size depended on their spatial organization. The above materials can be used as scaffolds for mesenchymal stem cells for creation of tissue engineering implants. The scaffold size and structure should be determined by the defects in the organs in which the regeneration processes have to be stimulated.

CHARACTERISTICS OF TUMORS THAT DEVELOPED IN MICE AFTER TREATMENT WITH IRRADIATED SYNGENEIC MESENCHYMAL STEM CELLS OF BONE MARROW.

Mesenchymal stem cells (MSCs) are present in almost all organs and tissues of the organism. It is believed, that MSCs could be transformed into cancer stem cells spontaneously or under influence of genotoxic factors and trigger the growth of tumors. The aim of this work was to study the possibility of malignant transformation of cultured MSCs from murine bone marrow (MSCs-BM) after g-irradiation in vitro and characterize of biochemical and histological features of the tumors that developed after transplantation of MSCs-BM into syngeneic mice. Tumors were observed in 3­4 months after MSCs-BM transplantation. After administration of MSCs-BM irradiated at a dose of 1 Gy, tumors were seen in 2 of 5 mice. After transplantation of MSCs-BM irradiated at a dose of 6 Gy, tumors were found in all 5 of 5 mice. In the case of control MSCs-BM, only one tumor appeared in 6 months after transplantation. The telomerase activity was two times higher in the tumor developed from 6 Gy irradiated MSCs-BM than from 1 Gy irradiated MSCs-BM. The tumors developed from control and irradiated MSCs-BM were classified as multicomponent mesenchymomas («mixture of sarcomas¼). Histological examination showed that tumors contained tissue areas of different histogenesis. Thus, MSCs-BM g-irradiated at doses of 1 and 6 Gy and, much less frequently, control MSCs-BM can transform into tumor cells and induce development of multicomponent mesenchymomas.

Migration and Proliferative Activity of Mesenchymal Stem Cells in 3D Polylactide Scaffolds Depends on Cell Seeding Technique and Collagen Modification.

We analyzed viability of mesenchymal stem cells seeded by static and dynamic methods to highly porous fibrous 3D poly-L-lactide scaffolds with similar physical and chemical properties, but different spatial organization modified with collagen. Standard collagen coating promoted protein adsorption on the scaffold surface and improved adhesive properties of 100 µ-thick scaffolds. Modification of 600-µ scaffolds with collagen under pressure increased proliferative activity of mesenchymal stem cells seeded under static and dynamic (delivery of 100,000 cells in 10 ml medium in a perfusion system at a rate of 1 ml/min) conditions by 47 and 648%, respectively (measured after 120-h culturing by MTT test). Dynamic conditions provide more uniform distribution of collagen on scaffold fibers and promote cell penetration into 3D poly-L-lactide scaffolds with thickness >600 µ.

Chitosan as a Modifying Component of Artificial Scaffold for Human Skin Tissue Engineering.

We compared the structure and mechanical properties of scaffolds based on pure collagen, pure chitosan, and a mixture of these polymers. The role of the composition and structure of scaffolds in the maintenance of cell functions (proliferation, differentiation, and migration) was demonstrated in two experimental models: homogeneous tissue analogues (scaffold populated by fibroblasts) and complex skin equivalents (fibroblasts and keratinocytes). In contrast to collagen scaffolds, pure chitosan inhibited the growth of fibroblasts that did not form contacts with chitosan fibers, but formed specific cellular conglomerates, spheroids, and lose their ability to synthesize natural extracellular matrix. However, the use of chitosan as an additive stimulated proliferative activity of fibroblasts on collagen, which can be associated with improvement of mechanical properties of the collagen scaffolds. The effectiveness of chitosan as an additional cross-linking agent also manifested in its ability to improve significantly the resistance of collagen scaffolds to fibroblast contraction in comparison with glutaraldehyde treatment. Polymer scaffolds (without cells) accelerated complete healing of skin wounds in vivo irrespective of their composition healing, pure chitosan sponge being most effective. We concluded that the use of chitosan as the scaffold for skin equivalents populated with skin cells is impractical, whereas it can be an effective modifier of polymer scaffolds.

[Assessment of the impact of GMO of plant origin on rat progeny development in 3 generations].

The publication presents the results of assessment of impact of genetically modified (GM) maize Liberty Link on prenatal and postnatal development of progeny of 3 generations of Wistar rats. A total of 630 adult animals and 2837 pups were used in the experiment. The animals were divided into 5 groups which got the diets with inclusion of maize: the animals of the experimental group got the diet with the GM-maize, animals of the control group - with near isogenic conventional analogue of the GM-maize, animals of the 1st, 2nd and 3rd reference groups - conventional varieties of maize ROSS 144 MV, ROSS 197 MVW, Dokuchayevskaya 250 MV respectively. The maize was included in the diet at maximum possible level not violating the balance of basic nutrients. Analysis of the data obtained during the study did not reveal any impact of GM-maize on rat progeny development.

[Effect of genetically modified plants on the development of rat progeny].

The paper presents the results of evaluating the effect of genetically modified (GM) maize on the prenatal and postnatal development of rat progeny in three generations. An experiment used 280 adult rats (160 females and 120 males) and 1545 infant rats of the first month of life. The animals were divided into 2 groups: 1) those given a diet including GM maize (an experimental group); 2) those fed on its isogenic control (a control group). The maize was included into the diet in maximally possible amount that did not impair the balance of essential nutrients (31.4% caloric value). Analysis of the data obtained from studies of the prenatal (preimplantation and postimplantation death and fetal somatometric parameters) and postnatal (physical development, survival, changes in somatometric parameters) development of rat offspring revealed no effect of GM maize as compared to the isogenic control. All the parameters were in the normal physiological range typical of the animals of this species and age. Thus, dietary intake of the given amount of GM maize had no impact on rat progeny development.

[Medical and biological safety assessment of genetically modified soybean event MON 89788. Report 1. Toxicologo-hygienic examinations].

The results of toxicologo-hygienic examinations, which were conducted within the framework of integrated medical and biological assessment of genetically modified second generation soybean event MON 89788, are presented. Analysis of morphological, hematological, biochemical parameters and system (sensitive) biomarkers has not confirmed any toxic effect of soybean event MON 89788.

[Medical and biological safety assessment of genetically modified maize strain MIR604].

The results of toxicologo-hygienic examinations, which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.-protected maize event MIR604, are presented. Analysis of morphological, hematological, biochemical parameters and system (sensitive) biomarkers has not confirmed any toxic effect of maize event MIR604.

[Medical and biological safety assessment of genetically modified maize event MON 88017. Report 1. Toxicologo-hygienic examinations].

The results of toxicologo-hygienic examinations, which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.--protected and glyphosate tolerant maize event MON 88017, are presented. Analysis of morphological, hematological, biochemical parameters and system (sensitive) biomarkers has not confirmed any toxic effect of maize event MON 88017.

[Morphological variants of neutrophilic granulocytes in blood of practically normal humans]. / Morfologicheskie varianty neitrofil'nykh granulotsitov krovi prakticheski zdorovykh liudei.

Verification of presumed inertness of blood neutrophil granulocytes revealed their morphological heterogeneity in practically healthy donors. At light microscopic level it was expressed as a varying degree of cell cytoplasm granularity--58% of the cells were highly granular, 30% contained moderate amount of granules and 12% were completely devoid of granules. According to the ultrastructural analysis, neutrophils were subdivided into four groups: intact cells (60%), cells with slight (26%), moderate (12%) and severe (2%) changes. The criteria for this classification included changes in neutrophil shape and ultrastructure during its activation: formation of pseudo- and lobopodia, spatial redistribution of organelles, degranulation etc. Presence of neutrophils with the signs of activation in the circulation suggests that the neutrophil system normally is not inert, but is in a state of so-called working tone, thus providing high antibacterial resistance of the macroorganism exposed to natural bacterial environment.

[Ultrastructural characteristics of nonphlogogenic and phlogogenic reaction of mono- and polynuclear phagocytes in their interaction with Staphylococcus aureus]. / Ultrastrukturnaia kharakteristika neflogogennogo i flogogennogo reagirovaniia mono- i polinuklearnykh fagotsitov pri ikh vzaimodeistvii so Staphylococcus aureus.

Antibacterial function of neutrophil leukocytes and peritoneal macrophages in their interaction with massive doses of Staphylococcus aureus (25 x 10(6) and 25 x 10(8) microorganisms) has been studied in the experiment in vivo. Two types of antibacterial reaction of phagocytes has been found, i.e. nonphlogogenic (physiological) and phlogogenic (inflammatory). nonphlogogenic type was characterized by marked antibacterial influence of phagocytes. phlogogenic reaction was accompanied by an increase of failure of phagocyte function, by their self-damage and break-up that leads to a decrease of their antibacterial activity followed by the inflammation.

[Non-inflammatory form of neutrophil antibacterial response]. / Nevospalitel'naia forma antibakterial'nogo reagirovaniia neitrofil'nykh leikotsitov.

According to the Mechnikov theory inflammation is the only form of the protective-adaptive response of phagocytes and phagocytosis is its essence. High doses of Staphylococcus aureus (25 x 10(6) and 25 x 10(2) bacteria) in the absence of additional peritoneal damage do not produce the inflammation. The organism of the highest animals possess non-phlogogenic mechanisms of protection against bacteria when the phagocyte function is not the destruction of bacteria but their catching and transportation to the intestinal lumen.

[Ultrastructural characteristics in neutrophilic leukocytes in patients with sepsis]. / Ultrastrukturnaia kharakteristika neitrofil'nykh leikotsitov krovi bol'nykh s sepsisom.

Electron microscopic studies of neutrophilic leukocytes from patients with sepsis have revealed that substantial counts of these cells are prone to degradation just in the blood, the organelles of the degraded cells many of which may be identified are present in the blood plasma. The degradation of neutrophilic leukocytes in systemic circulation may be one of the morphological signs of sepsis.

[Blood neutrophilic leukocytes in patients with suppurative-septic diseases]. / O sostoianii neitrofil'nykh leikotsitov krovi bol'nykh gnoino-septicheskimi zabolevaniiami.

Neutrophil leucocytes of patients with sepsis, purulent inflammatory processes clinically close to sepsis and those of healthy persons were studied electron-microscopically. Leucocytes with degranulation due to the release of their content into the circulation were found in purulent-inflammatory diseases. Leucocytes with pronounced degranulation, areas with cytoplasma lysis and extracellular organelles (lipid droplets, primary and secondary granules with clear-cut membrane borders and content of granules without membrane borders) were observed in sepsis.