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     

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     

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     

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     

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     

Stromal regulation of hemopoietic stem cells in long-term human bone marrow tissue cultures under the effect of parathyroid hormone

We studied the interaction between different categories of hemopoietic precursors with parathyroid hormone-activated stromal microenvironment. Improved survival of early precursors capable long-term hemopoiesis maintenance and increased number of later short-term repopulating precursors was demonstrated on the model of co-culturing of human bone marrow cells on a layer of adherent cells of long-term bone marrow cultures treated with parathyroid hormone. These changes correlate with increased expression of genes involved in the maintenance of the hemopoietic stem cells in the sublayer activated by parathyroid hormone. Simultaneously, the expression of some stromal differentiation genes, adhesion molecules for hemopoietic stem cells, and growth factors increased in adherent cell layers treated with parathyroid hormone. These findings attest to activating effect of parathyroid hormone on cells forming the niches for both early and later hemopoietic precursors, and hence parathyroid hormone can be used as a potential agent promoting expansion of early hemopoietic stem cells ex vivo. __________ Translated from Kletochnye Tekhnologii v Biologii i Medicine, No. 4, pp. 218–222, December, 2006     

Functional activity of hemopoietic and stromal cells in various types of myelodysplastic syndrome

Using clonal methods for assessment of hemopoietic and stromal cells and long-term bone marrow cell cultures, we have demonstrated heterogeneity of myelodysplastic syndrome. Low content of stromal precursor cells in native bone marrow, peculiarities in the formation of the stromal layer and its hemopoiesis-stimulating capacity in long-term cultures, and altered properties of stromal precursor cells in long-term cultures indicate defect in the stromal microenvironment in myelodysplastic syndrome. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 14–18, January, 1999     

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     

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     

Effect of dimethylsulfoxide on the functions of mesenchymal and hemopoietic precursors

The effects of dimethylsulfoxide on the state of mesenchymal precursors in vivo were demonstrated. Treatment with dimethylsulfoxide reduced the content of stromal clonogenic elements in the bone marrow and inhibited mobilization of mesenchymal precursors induced by granulocyte colony-stimulating factor. In in vitro system, dimethylsulfoxide inhibited proliferation of fibroblast, erythroid, and granulomonocytic colony-forming units and stimulates maturation of hemopoietic precursors. __________ Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 2, pp. 99–103, April, 2007     

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     

Defective adhesion and homing of hemopoietic precursors from the bone marrow of patients with myelodysplasia to stromal cells of normal bone marrow cultures

Hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome were characterized by lower adhesion to normal stromal sublayer compared to bone marrow precursors from healthy donors, while adhesion to fibroblast monolayer and fibronectin was similar in bone marrow cells from patients and donors. In vitro experiments showed that the percentage of adherent hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome in normal stromal sublayer and fibroblasts was lower compared to healthy donors. The decrease in adhesive activity of hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome probably contributes to impairment of cell-cell interactions in the bone marrow of these patients.__________This revised version was published online in August 2005 with the addition of the issue titleTranslated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 1, pp. 11–14, January, 2005     

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     

Changed homing of hemopoietic precursor cells after long-term treatment with parathyroid hormone

Changes in the capacity of hemopoietic stromal microenvironment to promote homing of hemopoietic stem cells from different hierarchical compartments were evaluated in mice treated with parathyroid hormone by determining their 24-h precipitation factor. This parameter did not change for splenic short-living hemopoietic stem cells (splenic CFU) and considerably decreased for the bone marrow of mice treated with parathyroid hormone. For earlier long-living hemopoietic stem cells (cells forming the cobblestone area on day 28) the precipitation factor after injections of parathyroid hormone did not change in the bone marrow and decreased in the spleen. These data suggest that parathyroid hormone decreases the efficiency of homing of short-living hemopoietic stem cells in the bone marrow. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 97–100, July, 2006     

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     

Changes in the hemopoietic system of mice deficient for tumor necrosis factor or lymphotoxin-α

Hemopoietic and stromal precursor cells were studied in mice deficient for tumor necrosis factor or lymphotoxin-α. In normal hemopoiesis the main characteristics of hemopoiesis in knockout mice did not differ from those in wild-type mice. Implantation of bone marrow cells from mice deficient for tumor necrosis factor onto irradiated sublayer of allong-living bone marrow culture led to a notable increase in the number of mature cells and granulocytic-macrophage precursor cells. This can be due to the fact that tumor necrosis factor inhibits proliferation of hemopoietic precursor cells, while in the absence of this factor precursor cells actively proliferate. On the other hand, cell composition and number of colony-forming units of granulocytes-macrophages are significantly decreased in cultures onto which bone marrow cells from lymphotoxin-α-deficient mice were implanted. This can be explained by impaired expression of adhesion molecules in these animals. In addition, the number of stromal precursor cells was changed in mice deficient by genes of the tumor necrosis factor cluster. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 76–79, July, 2000     

Changes in the hemopoietic system of mice deficient for tumor necrosis factor or lymphotoxin-alpha

Hemopoietic and stromal precursor cells were studied in mice deficient for tumor necrosis factor or lymphotoxin-α. In normal hemopoiesis the main characteristics of hemopoiesis in knockout mice did not differ from those in wild-type mice. Implantation of bone marrow cells from mice deficient for tumor necrosis factor onto irradiated sublayer of allong-living bone marrow culture led to a notable increase in the number of mature cells and granulocytic-macrophage precursor cells. This can be due to the fact that tumor necrosis factor inhibits proliferation of hemopoietic precursor cells, while in the absence of this factor precursor cells actively proliferate. On the other hand, cell composition and number of colony-forming units of granulocytes-macrophages are significantly decreased in cultures onto which bone marrow cells from lymphotoxin-α-deficient mice were implanted. This can be explained by impaired expression of adhesion molecules in these animals. In addition, the number of stromal precursor cells was changed in mice deficient by genes of the tumor necrosis factor cluster. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 76–79, July, 2000     

Role of Thy 1,2<Superscript>+</Superscript> Cells in the Regulation of Hemopoiesis during Experimental Neuroses

We studied the direct and stromal cell-mediated effects of bone marrow Thy 1,2⁺ cells on the growth of granulocyte-macrophage and erythroid colonies from the bone marrow of CBA/CaLac mice with experimental neuroses (conflict situation and paradoxical sleep deprivation). Proliferation and differentiation of hemopoietic precursors during neuroses are controlled by regulatory T cells. In conflict situation Thy 1,2⁺ cells stimulate the growth of hemopoietic precursors, which is associated with their direct effect and interaction with adherent cells of the hemopoiesis-inducing microenvironment. The interaction of Thy 1,2⁺ cells with adherent bone marrow cells during paradoxical sleep deprivation stimulates the formation of only granulocyte-macrophage colonies.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 6, pp. 608–612, June, 2005     

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.     

Effect of cytostatics on bone marrow stem cells

Morphological composition of the bone marrow, content of hemopoietic precursors, intensity of their proliferation and differentiation, and the size of mesenchymal precursor pool were studied in experiments on CBA/CaLac mice with myelosuppression induced by adriamycin, cyclophosphamide, or 5-fluorouracil in the maximum tolerated doses. The dynamics of changes in the content of granulomonocyte precursors in the bone marrow after cytostatic treatment was similar to that of erythroid precursors. Changes in the content of stromal mechanocytes were specific for each cytostatic. Different character of the reaction of the hemopoietic and mesenchymal stem cells to the test cytostatics was demonstrated.__________This revised version was published online in July 2005 with the addition of the issue title and article categoryTranslated from Kletochnye Tekhnologii v Biologii i Meditsine, Vol. 1, No. 1, pp. 20–24, January, 2005