Age-specific features of formation of hemopoietic microenvironment by stromal precursors from bone marrow of thymectomized mice

Heterotopic transplantation of bone marrow demonstrated that the content of stromal precursor cells capable of hemopoietic microenvironment transfer does not depend on thymus function. Thymectomy of bone marrow donors involves a decrease in the size of foci formed in young donors and an increase in old recipients. The results indicate a thymus-dependent regulation of proliferation of stromal precursors and/or their factor-sensitive category, determining the proliferation of recirculating stem hemopoietic cells. The size of ectopic hemopoiesis focus depends on the age of recipient. Transplantation of syngeneic thymus under renal capsule of thymectomized mice abolished the effect of thymectomy. Osteogenic activity of stromal precursors correlates with the age of bone marrow donors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 4, pp. 457–459, April, 1998     

Effect of leukemia inhibitory factor on hemopoietic and stromal precursor cells in prolonged culture of mouse bone marrow

Treatment of prolonged bone marrow cultures with leukemia inhibitory factor during the first 2 weeks after explantation has no appreciable effect on the production of precursors and mature hemopoietic cells during 4 weeks of culturing. However, the proliferative potential of polypotent hemopoietic precursors in these cultures increases substantially. The addition of exogenous cytokine has a pronounced effect on the hemopoietic stroma, specifically, on the content of osteogenic precursors and cells transporting the hemopoietic microenvironment to prolonged bone marrow cultures treated by leukemia inhibitory factor. This effect is confirmed by formation of ectopic hemopoietic fociin vivo, being 2–3 times higher than in the control. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 9, pp. 325–328, September, 1996     

Hemopoietic microenvironment-transferring units and inducible hemopoietic stromal precursors in the bone marrow of thymectomized mice

The method of heterotopic transplantation of the bone marrow was used to study the effect of thymectomy on clonogenic and inducible hemopoietic stromal precursors in adult rats. The self-maintenance or clonogenic capacity of stromal precursors was evaluated by retransplantation of primary hemopoietic foci. The kinetics of the formation of ectopic foci from thymectomized rats is similar to that of normal bone marrow. The presence of inducible stromal hemopoietic precursors was evaluated by the stimulation index (the ratio of the size of hemopoietic focus formed in irradiated to that in nonirradiated recipient). It is found that the growth of ectopic focus in chimeras is stimulated by a nonthymic factor, which suggests thymus-independent regulation of hemopoietic microenvironment precursor cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 186–189, February, 1999     

Effect of cytokines (G-CSF and SCF) on stromal precursor cells

Repeated injections of hemopoietic cytokines (granulocyte colony-stimulating factor and stem-cell factor) to normal mice increase the content of bone marrow stromal precursors, which are capable of transferring hemopoietic microenvironment; cytokines have no effect on osteogenic potencies of stromal precursors. In contrast, injection of granulocyte colonystimulating factor during organization of a hemopoietic microenvironment considerably decreases the number of stromal precursors in the ectopic focus. The role of these stromal effects of cytokines in cytokine-induced mobilization of stem cells from the bone marrow into circulation remains unclear. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 204–206, February, 1998     

Proliferative activity of early hemopoietic precursors under conditions of increased and decreased activity of protein kinase C in mouse bone marrow

Activation of protein kinase C (transfer from cytosol to cell membranes) with phorbol ester increases proliferation of splenic colony-forming units in the bone marrow. Subsequent incubation of bone marrow cells with the factor inhibiting proliferative activity of early hemopoietic precursors results in the recovery of protein kinase C activity in cell cytosol and a decrease in proliferative activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 11, pp. 541–543, November, 1997     

Correction of testosterone-induced changes in a population of hemopoietic precursors by a bone-marrow inhibitor of the proliferative activity of a hemopoietic stem cell

A factor inhibiting the proliferation of splenic colony-forming units, injected bothin vivo and after preincubation of mouse bone marrow cellsin vitro, had a dose-dependent effect on the increased proliferative activity of splenic colony-forming units from the bone marrow of mice treated with testosterone propionate. This was associated with a reduction in the number of early hemopoietic precursors of mouse bone marrow. The counts of clonogenic granulocytic-macrophagal and macrophagal colony-forming units decreased and that of burst-forming units in murine bone marrow increased after exposure to the hormone. Testosterone propionate promoted a decrease of the repopulating potential of bone marrow cells, which recovered after their preincubation with the factor inhibiting the proliferation of splenic colony-forming units. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 10, pp. 394–397, October, 1995     

Functional capacities of committed hemopoietic progenitor cells of the bone marrow in AKR/JY mice during the preleukemia period

The content of hemopoietic progenitor cells in 7-month-old AKR/JY mice was higher than in hybrid (CBA/CaLacxAKR/JY)F1 mice of the same age. After stress, the number of erythroid precursors in leukemia-prone mouse strain and hybrids increased, while the content of other precursors in AKR/JY mice (by contrast to that in (CBA/CaLacxAKR/JY)F1 mice) decreased. Thus, functional capacity of the pool of bone marrow committed hemopoietic precursors in AKR/JY mice is reduced during the preleukemia period. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 578–581, November, 1999     

Dependence of the proliferation of hemopoietic adrenergic precursors under the influence of cytostatics

After administration of 5-fluorouracil in a high dose (114 mg/kg), the proliferation of committed precursors of erythro- and granulomonocytopoiesis is controlled by sympatheticoadrenal system. On the one hand, catecholamines facilitate, predominantly via β-structures, the migration of Thy-1⁺-cells that stimulate hemopoietic precursors for the S-phase of cell cycle. On the other hand, sympatheticoadrenal transmitters potentiate via β- and α-adrenoreceptors the suppressor activity of the cytostatic on the growth and maturation of erythropoietic and, to a lesser extent, granulocytopoietic precursors. These factors may contribute to the process of long restoration of the granulocyte and, to a higher extent, erythrocyte stem cells in the bone marrow after a high dose of 5-fluorouracil. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 638–641, June, 1997     

Expression of bone marrow macrophage receptors in cytostatic-induced myelodepression

Expression of macrophage sialoadhesin and erythroblast receptors involved into the hemopoietic islet formation is studied in cyclophosphamide-treated CBA mice. The number of hemopoietic islets and the content of immature granulocytic and erythroid cells were determined. Cyclophosphane reduces the expression of sialoadhesin and erythroblast receptors. It can be hypothesized that the disturbances in granulocyte differentiation result from impaired sialoadhesin-mediated interaction between hemopoietic cells and macrophages. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 7, pp. 25–27, July, 1998     

Effects of prenatal hypoxia on the formation of immune deficiency in newborn mice

Fetal hypoxia in the II trimester of pregnancy caused immunodeficiency in newborn mice: inhibition of antibody production to sheep erythrocytes and disturbances in migration of early hemopoietic precursors from the bone marrow to the spleen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp. 664–666, June, 2000     

Mechanisms of hemostimulating effect of glycyrram

Glycyrram is a plant preparation containing 2d-glucuronic acid residues, a component of extracellular matrix of the bone marrow. Glycyrram is shown to stimulate restoration of granulomonocyto- and erythropoiesis under conditions of cytostatic myelosuppression induced by 5-fluorouracil or cyclophosphamide. The preparation elevates the contents of both morphologically discernible elements and committed precursors. Myelotropic effect of glycyrram is not related to its direct action on hemopoietic cells but depends on stimulation of hemopoietic microenvironment. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 5, pp. 555–559, May, 1997     

Effects of adrenal glands on bone marrow hemopoietic microenvironment

Effects of bilateral adrenalectomy on the hemopoiesis-inducing microenvironment and bone marrow hemopoietic cells were studied. It was shown that adrenal hormones regulate secretory activity of the hemopoiesis-inducing microenvironment, in particular its nonadherent fraction. Adrenalectomy did not change the content of hemopoietic islets, number of erythro- and granulocytopoietic precursors, and blood indexes. The data suggest that structural and functional properties of the hemopoiesis-inducing microenvironment determined by the great variety and high plasticity of organ and intersystem regulatory interactions for a long time compensate the effects of hypocorticism on the requirements for mature blood cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 586–590, November, 1999     

Effects of exogenous glucocorticoids on colony-forming activity of the bone marrow under cytotoxic exposure

Experiments on CBA/CaLac mice receiving a half-maximum tolerated dose of 5-fluorouracil demonstrated an inhibitory effect of physiological concentrations of dexamethasone (127×10⁻⁹M) on colony-forming activity of erythroid and granulomonocytic precursors in intact and regenerating bone marrow. Dexamethasone exhibited protective effects on granulocyte, macrophage, and fibroblast precursors during maximum myelosuppression. Various responses of hemopoietic progenitor cells to exogenous corticosteroidin vitro are probably determined by their functional state. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 412–414, April, 1999     

Effect of Adrenomimetics and Serotonin on Polypotent Stromal and Hemopoietic Precursors in Cytostatic Myelosuppression

Effects of serotonin and adrenomimetics (phenylephrine and isoprenaline) on bone marrow stromal and polypotent hemopoietic precursors were studied in vitro on the model of cyclophosphamide- induced myelosuppression. It was found that under conditions of myelosuppression, adrenomimetics potentiate differentiation of polypotent hemopoietic precursors into mature precursors (granulocyte-macrophage and granulocyte CFU) initiated by granulocytic CSF, while serotonin suppresses these processes. Adrenomimetics (especially, isoprenaline) abolish high rate of division of stromal precursors and suppress the growth of granulocytic CSF induced by fibroblast-like cells. Serotonin does not affect proliferation of stromal precursors, but potentiates the granulocytopoiesis-stimulating effects of fibroblasts.     

Adaptive capacity of granulocytic bone marrow stem cells in preleukemic AKR mice

In leukemia-prone AKR mice, adaptation to 10-h immobilization stress increases the content of sialoadhesin-positive macrophages to the level of intact (CBA×AKR)F₁ hybrids. Hybrid mice responds to stress by a slight reduction of this parameter. The contents of granulocytic hemopoietic islets and committed granulomonocyte precursors in the bone marrow after stress undergo opposite changes. Unlike hybrids, granulocytopoiesis in AKR mice is not activated by stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 151–154, February, 1999     

Functional disturbances in hemopoietic microenvironment in various forms of myelodysplastic syndrome

We studied the ability of stromal sublayer of long-term bone marrow cultures and peripheral blood macrophages from patients with various forms of myelodysplastic syndrome to maintain the growth of normal granulocyte-macrophage colony-forming units in mixed cultures. There were changes in the hemopoietic microenvironment in these patients: decreased cellularity of the bone marrow and impaired formation of sublayers in long-term bone marrow cultures, production of growth factors, maintaining the growth of normal granulocyte-macrophage precursors by stromal cells. Dysfunction of macrophages in the stromal microenvironment was probably related to the presence of pathological macrophages. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 255–258, September, 2000     

Participation of humoral factors in the regulation of hemopoiesis in cytostatic myelodepression

Production of hemopoietic factors responsible for colony-stimulating and erythropoietic activities by hemopoietic microenvironment is measured and the serum level of these activities in CBA mice treated with various cytostatics is determined. It is shown that the key role in direct stimulation of suppressed hemopoiesis is played by hemopoietic growth factors produced by adherent and nonadherent cells of hemopoietic microenvironment. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 161–165, August, 1997     

Development of endocrine and lymphocytopoietic functions of the thymus in human embryogenesis

The endocrine function of the thymus develops earlier than lymphocytopoietic. Thymalin is produced by epithelial cells in the thymus primordium. It is released into the blood and regulates differentiation of T lymphocytes in the liver, the initial hemopoietic organ. The hormonal and lymphopoietic functions of human thymus are united on weeks 7.5–8 of embryonic life. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 453–456, October, 2000     

Functional disturbances in hemopoietic microenvironment in various forms of myelodysplastic syndrome

We studied the ability of stromal sublayer of long-term bone marrow cultures and peripheral blood macrophages from patients with various forms of myelodysplastic syndrome to maintain the growth of normal granulocyte-macrophage colony-forming units in mixed cultures. There were changes in the hemopoietic microenvironment in these patients: decreased cellularity of the bone marrow and impaired formation of sublayers in long-term bone marrow cultures, production of growth factors, maintaining the growth of normal granulocyte-macrophage precursors by stromal cells. Dysfunction of macrophages in the stromal microenvironment was probably related to the presence of pathological macrophages. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 255–258, September, 2000     

Structural and functional organization of bone marrow of AKR/J mice during aging

Expression of sialoadhesin and erythroblast receptors on macrophages and structural and functional organization of the bone marrow during aging were studied on AKR/J mice. It is shown that progressive accumulation of granulocyte hemopoietic islets can be a compensatory reaction to a decreased capacity of their central stromal elements to bind young granulocytopoietic cells. Expression of erythroblast receptors on macrophages from 4-month-old AKR/J mice is considerably higher than in young and old mice and than in 4-month-old (CBA×AKR)F₁ mice. The high concentration of erythroid precursors in the bone marrow of AKR mice is not accompanied by enhanced erythropoiesis, probably due to a decreased yield of erythroid hemopoietic islets. Thus, a marked imbalance in structural and functional organization of the bone marrow during aging is noted in highly leukemic AKR/J mice, which provides a basis for the development of reliable diagnostic and prognostic criteria of leukemic progression. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 3, pp. 266–268, March, 1998