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     

Effects of bone marrow conditioned media on proliferation of stromal clonogenic cellsin vitro

Fibroblast growth factors aFGF, bFGF, IGF-I, IGF-II, TGF-β, EGF, and PDGF did not stimulate the formation of stromal fibroblast colonies (CFC-F-colonies) in cultured murine adhesive bone marrow cells. It means that colony-stimulating activity of the bone marrow feeder cells with respect to the formation of stromal fibroblast colonies does not depend on the known growth factors. A scheme and conditions of culturing are developed for preparing conditioned media from bone marrow cell cultures which can replace the CFC-F colonystimulating activity of the bone marrow feeder cellsin vitro. Primary separation of conditioned media by ultrafiltration reveals that only the fraction with molecular weight of more than 65 kD exhibits CFC-F colony-stimulating activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 218–220, February, 1999     

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     

Radiometric evaluation of the effect of xenobiotics on proliferation of bone marrow cells in mice

A radiometric method of evaluating the effect of chemical compounds on the proliferative activity of bone marrow cells is described which consists of measuring the incorporation of labeled³H-thymidine in DNA. Results are reported on a comparative study of the effect of known immunotropic substances on bone marrow cell proliferation using the present method and the method of evaluating endogenous colony formation. Analysis of the results obtained by two variants ofin vivo andin vitro experiments provides additional information regarding the mechanism of action of the substances. Translated fromByulleten Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 222–224, August, 1995 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Role of Thy 1.2+ cells in hemopoietic regulation in cytostatic-induced hemosuppression

Effect of Thy 1.2⁺ cells (direct and mediated by stromal elements) on the growth of granulomonocyte and erythroid colonies in the bone marrow is studied on CBA mice with cytostatic disease induced by single injection of adriamycin, cyclophosphamide, and 5-fluorouracil in maximum permissible doses. It is shown that Thy 1.2⁺ cells stimulate colony formation in regenerating bone marrow, the effect depending on functional activity of hemopoiesis-inducing microenvironment. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol 125, No. 5, pp. 509–513, May, 1998     

Effects of immunization with group a streptococcal antigens on the transplantability of mouse bone marrow stromal stem cells, counts of stromal precursor cells, and their osteogenic characteristics

Immunization of CBA mice with killed group A streptococcus (type 5) vaccine changed the counts of stromal precursor cells (CFC-F) in bone marrow transplants at different donorrecipient combinations (normal, N, or immune, I). CFC-F counts in bone marrow transplants from normal mice transplanted to immunized animals decreased 4-6-fold depending on the transplant age in comparison with similar transplants in normal recipients. The percentage of CFC-F colonies with alkaline phosphatase (osteogenesis marker) activity decreased more than 2-fold. Similarly, the count of CFC-F in the transplants was 2-fold lower during delayed (7 months) period after bone marrow transplantation from immunized donors (8–12 days after the end of immunization) to intact recipients, while 2 months after transplantation it was 3-fold lower. The mean optical density of the bone capsule in preparations stained for glycogen and alkaline phosphatase was 1.5-3 times lower in the N → I and I → N experiments in comparison with the control (N → N). On the other hand, CFC-F count in the femoral bone marrow of immunized animals was significantly (3.5-2.5 times) higher during the period from 8 days to 8 months after the end of immunization compared to CFC-F count in the femoral bone marrow of intact mice. These results attest to a significant prolonged effect of streptococcal antigens on the bone marrow stromal tissue. These data also indicate that not all CFC-F, the counts of which increased in response to antigens, are responsible for transplantability of the stromal tissue in heterotopic transplantation. Immunization by streptococcal antigens seemed to suppress transplantability and osteogenic activity of stromal stem cells. The efficiency of CFC-F cloning in mouse bone marrow cultures increased significantly (2-3-fold) in the presence of sera from immune mice. The levels of TNF-α and IFN-γ were low in this serum (2.7 and 6 times lower, respectively) in comparison with normal serum. Presumably, the effects of streptococcal antigens on stromal tissue were mediated through serum cytokines.     

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     

Counts of Stromal Precursor Cells in Heterotopic Bone Marrow Transplants in Mice Immunized with Group A Streptococcus Antigens

The count of stromal precursor cells in bone marrow transplants from CBA mice, transplanted to animals immunized with killed type 5 group A streptococcus vaccine, decreased 4.5–6.5 times (depending on the transplant age) in comparison with the grafts transplanted to normal recipients. The counts of stromal precursor cells in 1.5–3-month bone marrow transplants from animals immunized with killed streptococcal vaccine transplanted to normal mice were virtually the same, while in 7-month transplants they decreased 2-fold in comparison with their counts in bone marrow transplants from normal CBA mice transplanted to normal animals. The content of stromal precursor cells in the femoral bone marrow of animals immunized with killed streptococcal vaccine was appreciably (3.5 times) higher than in the bone marrow of normal mice. The results attest to an appreciable effect of streptococcal antigens on the bone marrow stromal tissue and suggest that not all stromal precursor cells, whose count increases after injection of antigens, are responsible for transplantability of the stromal tissue in case of its heterotopic transplantation. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 7, pp. 77–80, July, 2005     

Decrease of antitumor and suppressor activities of nonadherent bone marrow cells by culturing in medium conditioned with ehrlich adenocarcinoma cells

It was demonstrated that proliferation of bone marrow cells cultured in medium conditioned with tumor cells is somewhat increased. A much more potent stimulation of bone marrow cell proliferation is observed after the removal of cells carrying the erythroblast antigen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. N ^o 5, pp. 514–517, May, 1994 Presented by N. V. Vasil'ev, Member of the Russian Academy of Medical Sciences     

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     

Age-related changes in the content of stromal clonogenic cells in hemopoietic and lymphoid organs

The content of stromal clonogenic cells in hemopoietic and lymphoid organs of mice and guinea pigs decreases with age. This drop is most pronounced in the thymus of mice and guinea pigs and in mouse spleen (more than 12-, 75-, and 8-fold, respectively). The contents of stromal clonogenic cells in the bone marrow of old mice and in the spleen of old guinea pigs are reduced by 50 and 40%, respectively, in comparison with young animals. These data indicate that the content of committed and inducible osteogenic precursors can decrease with age. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 550–553, May, 1999     

Evaluation of graft-versus-host disease based on measurement of HLA levels in the plasma of allogeneic bone marrow recipients

HLA levels were estimated in the plasma of allogeneic bone marrow recipients with and without graft-versus-host disease (GVHD). It was found that the level of plasma-soluble HLA is elevated in recipients with developing acute GVHD and that a rise in these antigens coincides with the onset of clinically manifest GVHD. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 596–598, December, 1995     

Comparative morphometric and information analysis of the changes in different parts of the pancreas following ligation

The compensatory-adaptive changes in the guinea pig exocrine and endocrine pancreas following ligation are studied using morphometric and information methods. Objective criteria for evaluating organ changes are elaborated. The specific features of regeneration in exocrine and endocrine parts of the organ are described. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 86–88, January, 1995     

Heterophilic antibodies to connective tissue antigens in the blood sera of rheumatic patients do not cross-react with group AStreptococcus antigens

Heterophilic antibodies reacting with antigens of interstitial connective tissue of bovine myocardium were found in the sera of patients with rheumatic fever. These antibodies were referred to class IgG. Immunologic specificity of the reaction with these antigens was confirmed in experiments with F(ab′)₂ fragments from IgG isolated from the sera of rheumatic patients. Heterophilic antibodies were not adsorbed by various antigens of group AStreptococcus, nor were they isolated in a column with immunosorbent prepared on the basis of nontype-specific streptococcal antigens. The reaction of patients' sera was not inhibited by monoclonal antibodies to nontype-specific antigens cross-reacting with antigens of myocardial interstitial connective tisSue. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 6, pp. 642–644, June, 1994 Presented by S. V. Prozorovskii, Member of the Russian Academy of Medical Sciences     

Use of osteogenic bone-marrow precursor cells for reparative osteogenesis in the mandible of experimental animals

Using a model of “bony tissue tunnel defect” produced by the removal of a mandibular incisor in rats, it was found that closing the defect with a bioprosthesis prevented the washing out of osteogenic bone marrow precursor cells, which serve as a substrate for reparative osteogenesis, from the mandibular spongy bone. The reparative process was strongly stimulated if the bioprosthesis contained estrone; in this case, the time required for the tooth socket to be filled with osteogenic tissue was shortened by half. When no bone marrow elements were present in the socket, it was filled with fibrotic connective tissue, the number of bone marrow elements in spongy bone cavities was small, and the mandibular osteogenic tissue underwent atrophy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 72–75, January, 1995     

Platelet-Derived Growth Factor Requirement for Cultured Descendants of Rabbit Stromal Bone Marrow Precursors

Addition of irradiated bone marrow feeder from guinea pigs and rabbits to cultures of passed rabbit bone marrow fibroblasts considerably decreases the efficiency of colony-formation and the total amount of fibroblasts in cultures. The presence of irradiated rabbit blood platelets sharply increases these parameters. The addition of irradiated bone marrow feeder to rabbit bone marrow fibroblasts cultured under conditions promoting cell differentiation also decreases the total content of fibroblasts in cultures. Our results suggest that cultured descendants of rabbit bone marrow stromal precursors preserve both the sensitivity to inhibitory factors produced by bone marrow cells coexisting with stromal precursors in cultures (typical of stromal precursors of these animals) and high sensitivity to growth-stimulating platelet-derived factors (typical of stromal precursors from rabbits and other animal species).__________Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 113–116, 2005     

Effect of Serum from Mice Immunized with Group A Streptococcus Antigens on the Efficiency of <Emphasis Type="Italic">In Vitro</Emphasis> Cloning of Stromal Precursor Cells

The efficiency of cloning of stromal precursor cell in mouse bone marrow culture increases significantly (2–3-fold) in the presence of serum from mice immunized with type 5 group A streptococcus antigens (5-20 μl serum/ml culture medium) in comparison with intact animal serum. The levels of TNF-α and IFN-γ are significantly reduced (2.7 times and more than 6-fold, respectively) in the sera of immunized mice in comparison with normal serum. Serum levels of IL-2, -4, -5, -10, and -12 were about the same in both groups; no granulocyte-macrophage CSF was detected. These data attest to appreciable effect of immunization with streptococcal antigens on the bone marrow stromal tissue; this effect is presumably mediated through serum cytokines. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 663–666, December, 2008     

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