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T V Michurina

Publications and source records attributed to T V Michurina.

At least 19 recordsLinked to original sources

Studies on clonogenic hemopoietic cells of vertebrate in space: problems and perspectives.

Hemopoietic tissues were studied in vertebrates launched aboard the Soviet (Russian) biosatellites ("Cosmos-1129, 1514, 1667, 1887 and 2044"; "Bion-10 and 11") between 1980 and 1996. In the bone marrow of rats exposed to spaceflight conditions, a statistically significant decrease in cell number was revealed in the progenitor cell compartment accounting for the compensatory response of granulocyte-macrophage (CFU-gm) and erythrocyte lineages (BFU-e and CFU-e) and in the compartment of multipotent hemopoietic stem cells (CFU-s), which is responsible for the permanent renewal of hemopoietic tissue. The number of stromal fibroblastic progenitors (CFC-f) in the bone marrow of these rats was also reduced. Apparently, changes in the hemopoietic stroma damage the hemopoietic microenvironment and, hence, may be responsible for changes observed in the hemopoietic tissue proper. Attempts were made to develop methods for analyzing morphologically indiscernible clonogenic hemopoietic cells of newts, and studies on the effects of spaceflight factors on these cells were performed. The results showed that the numbers of clonogenic cells in newts of the flight group newts were significantly lower than in control newts. The data obtained are used as the basis for formulating the problems to be studied, drawing up a program for further research on the effects of spaceflight factors on stem and other clonogenic hemopoietic cells, and developing new experimental models for analyzing stem cells, the state of the hemopoietic stroma, etc.

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Experimental analysis of cell interactions during hemopoiesis.

The principal approach was to study hemopoiesis on different stromal cell underlayers (fibroblasts or fibroblast-like cells covering a foreign body implanted into the peritoneal cavity of mice or other rodents) after intraperitoneal transplantation of syngeneic, allogeneic, and xenogeneic hemopoietic cells. The data obtained are compared with the results of experiments on repopulation of ectopic hemopoietic territories (under the mouse kidney capsule) by syngeneic and xenogeneic hemopoietic cells. Competitive cell interactions are described that occur during repopulation of the hemopoietic stroma or formation of the hemopoietic foci on cellulose acetate membranes (CAMs) in the peritoneal cavity of irradiated mice by genetically different hemopoietic cells transplanted to these animals (multicomponent radiation chimeras). The model of xenogeneic and multicomponent radiation chimeras was reproduced in long-term bone marrow cultures, where hemopoietic cells of different genotypes coexisted, without any competitive cell elimination. The second part of this review deals with hemopoiesis on stromal cell underlayers, formed by cells of different origin, different stages of development, and obtained from other sources. These underlayers were formed on CAMs in vitro and then transferred into the peritoneal cavity of irradiated mice, which subsequently received intraperitoneal injections of donor hemopoietic cells. Specific features of hemopoiesis on stromal underlayers formed by the following cell types are described: (1) fibroblasts from mouse embryos at different developmental stages; (2) fibroblasts from the skin, liver, and bone marrow of 17-day mouse fetuses and newborn mice; (3) fibroblasts from the monolayer cultures of mouse and rat bone marrow; (4) 3T3 cell line; (5) hepatocytes of 17-day mouse fetuses or sexually mature rats; (6) newborn mouse kidney cells; and (7) cells transgenic for the erythropoietin gene. The phenomena observed in these experiments and their probable mechanisms are discussed.

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Blood and clonogenic hemopoietic cells of newts after the space flight.

Ribbed newts were used for studying the effect of space flight on board of the biosatellite (Cosmos-2229) on blood and clonogenic hemopoietic cells. In blood of newts of the flight group, the relative proportion of neutrophils increased, whereas that of lymphocytes and eosinophils decreased. Space flight did not result in loss of the ability of newt blood cells to incorporate H3-thymidine. Analysis of clonogenic hemopoietic cells was performed using the method of hemopoietic colony formation on cellulose acetate membranes implanted into the peritoneal cavity of irradiated newts. To analyze reconstitution of hemopoiesis after irradiation donor hemopoietic cells from flight or control newts were transplanted into irradiated newts whose hemopoietic organs were investigated. The newt can be considered an adequate model for studying hemopoiesis under the conditions of the space flight.

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Decrease in the number of progenitors of erythrocytes (BFUe, CFUe), granulocytes and macrophages (GM-CFC) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 Biosatellite.

A decrease in the number of progenitors of erythrocytes (BFUe, CFUe) and of granulocytes and macrophages (GM-CFC) in bone marrow was found in rats exposed to microgravitation during a 14-day flight onboard the Cosmos-2044 biosatellite when compared to control rats maintained under conditions of gravitation on the ground. The number of progenitors of both lineages of haemopoiesis was also decreased in synchronous control rats, thus suggesting that the pool of progenitors is influenced also by the action of the nonspecific space flight factors.

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Decrease in the number of progenitors of fibroblasts (CFUf) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 biosatellite.

A decrease in the number of progenitors of fibroblasts (CFUf) was found in bone marrow of rats that underwent a 14-day flight in the state of weightlessness onboard the Cosmos-2044 biosatellite, immediately after flight, when compared with rats maintained in control conditions of terrestrial gravitation. These changes may be explained by the action of specific factors of microgravitation.

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[Structure of ectopic foci of hematopoiesis in the mouse].

By means of light and electron microscopic methods foci of ectopic hemopoiesis have been investigated. They are formed on acetate-cellulose (AC) membranes implanted into the mice peritoneal cavity and into the mesentery after radiation and intraperitoneal injection of a donor's bone marrow. On the surface of the AC-membranes predominantly granulocytic differentiation of hemopoietic colonies is observed, prevalence of fibroblasts in the sublayer composition, absence of contacts of hemopoietic elements of the colonies with cells of the sublayer. In the mesentery mixed hemopoietic colonies of the donor's origin are revealed consisting of elements of granulocytic, macrophagal and megakaryocytic lines of differentiation. In the mesenteric colonies there are noted mesothelial cells, lipocytes, macrophages, and reticular cells having contacts with hemopoietic cells. The role of the sublayer cells for formation and differentiation of the hemopoietic foci in the experimental systems studied is discussed.

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[Stromal cells of the regenerating bone marrow in rats (an immunocytochemical electron microscopy study)].

Process of the bone marrow regeneration has been studied after its removal out of the rat femoral bone cavity. The stage of stroma formation precedes hemopoiesis. The stromal cells during its reconstruction (the 4th-5th day after removal of the bone marrow) are analyzed by means of the indirect immune-peroxidase electron microscopical method with antiserum applied against insoluble antigens of the rat bone marrow cells. Most of the stromal cells do not fix the antiserum used, as do the hemopoietic cells, macrophages and preosteoclasts. Some part of the stromal cells (not more than 30%) demonstrate the immune-peroxidase label. The labelled stromal cells have some ultrastructural signs of poorly differentiated elements of fibroblastic and osteoblastic raws. In the regeneration area, there are non-labelled poorly differentiated cells, which do not differ, at the ultrastructural level, from labelled poorly differentiated stromal elements. Possible causes of the difference revealed among the poorly differentiated stromal cells concerning their fixing of the anti-bone-marrow antiserum are discussed.

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[Origin of the phagocytes of the central nervous system].

Presence of cells having hemopoietic origin in an intact tissue and in the lesion focus in the brain of xenogenic (a rat and mice) radiative chimeras has been studied in order to elucidate the sources of phagocytes in the CNS and their relation to the microglial elements. To identify the cells of the hemopoietic origin in the xenogenic radiative chimeras, an indirect immunofluorescent method has been applied using a specific antiserum against nonsoluble antigens of the rat bone marrow cells. In the intact cerebral tissue of the xenogenic radiative chimeras no cells of the donor type have been revealed during one year after irradiation and bone marrow transplantation. The cells having hemopoietic origin (macrophages, leucocytes) are revealed in the lesion locus (inflammatory granuloma) and in the surrounding cerebral tissue. A suggestion is made that phagocytes in the CNS lesion focus are of hematogenic origin and that there is not any histogenic connection between the microglia and the system of mononuclear phagocytes.

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[Morphophysiological characteristics of the development and involution of mammary gland structures in murine radiation chimeras].

A study of development and involution of the mammary glands was carried out in syngeneic and xenogeneic mouse radiation chaimeras at different times after transplantation of the bone marrow cells, before and after restoration of the lymphoid tissue. The data obtained suggest the important role of the lymphoid (immune) component in the processes of development and involution of the mammary gland structures, as well the necessity of genetic homology of the hemopoietic elements and the mammary gland cells.

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[Cells of hematopoietic origin in the connective tissue of various organs in xenogeneic murine radiation chimeras].

The distribution of donor cells in the connective tissue of different organs of xenogeneic (rat in mouse) radiation chimaeras was studied under the normal conditions and upon its de novo formation. The donor cells were identified by means of indirect immunofluorescent method with the use of specific antiserum against surface antigens of the rat bone marrow cells. It was shown that macrophages of subcutaneous connective tissue, lung alveolar macrophages, Kuppfer's cells, macrophages of intestinal mucosa in the long living radiochimaeras were represented by the donor cells. The fibroblast-like cells of donor origin were found in the subcutaneous loose connective tissue, among the connective tissue elements of cross striated muscles, in the cardiac muscle, in the intestinal mucosa. The repopulation of Peyer's patches of the radiochimaeras by the donor cells was demonstrated. The macrophages of hemopoietic origin (donor origin) were found in the inflammatory granuloma in the brain cortex. The donor cells were found in the connective tissue of mammary glands following the hormonal stimulation. Differences were found with respect to binding of the antiserum used to cells of the capsule around the foreign body in different organs of xenogeneic chimaeras.

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[Origin of fibroblasts and macrophages of skin wound granulation tissue].

By the method of thymidine autoradiography and fluorescing antibodies, the origin of cells participating in healing the experimentally produced wounds was investigated. 3H-thymidine was administered a day before the production of the wounds. 14C-thymidine was injected impulsively 1 h before the material was fixed 1,3 and 8 days after the trauma. The analysis of the autographs demonstrated that during wound healing the cell-precursors of macrophages and fibroblasts migrate from beyond the limits of the connective tissue. By means of the fluorescing antibodies in mouse radiation xenogenic chimaeras it was demonstrated that macrophages and fibroblasts participating in wound healing take their origin from the donor's elements, that is, are of bone marrow origin.

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