New bone induction by demineralized bone matrix in immunosuppressed rats

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

Immunological recovery of thymectomized and sham-thymectomized lethally irradiated mice reconstituted with syngeneic bone marrow cells.

Immunological functions of lethally irradiated mice reconstituted with syngeneic bone marrow cells recover after 5--6 weeks. In mice that had been thymectomized before irradiation and reconstitution, T-cell function is deficient but the B-cell function is preserved.     

Experimental allergic encephalomyelitis in T-lymphocyte deficient rats.

Thymectomized, lethally irradiated rats reconstituted with syngeneic bone marrow were injected with rat brain in complete Freund adjuvant mixture. Both, they and sham-thymectomized, irradiated and bone marrow protected rats displayed a higher incidence of leg paralysis than normal non-irradiated animals. Thymectomy lowered the incidence of the disease.     

Experimental allergic encephalomyelitis in T-lymphocyte deficient rats

Summary Thymectomized, lethally irradiated rats reconstituted with syngeneic bone marrow were injected with rat brain in complete Freund adjuvant mixture. Both, they and sham-thymectomized, irradiated and bone marrow protected rats displayed a higher incidence of leg paralysis than normal non-irradiated animals. Thymectomy lowered the incidence of the disease.Supported by the Research Fund of Croatia (Zagreb).     

Immunological recovery of thymectomized and sham-thymectomized lethally irradiated mice reconstituted with syngeneic hone marrow cells

Summary Immunological functions of lethally irradiated mice reconstituted with syngeneic bone marrow cells recover after 5–6 weeks. In mice that had been thymectomized before irradiation and reconstitution, T-cell function is deficient but the B-cell function is preserved.Supported by subcontract No. 3322 from the Biology Division of Oak Ridge National Laboratory of the University of Tennessee, and by the Fulbright-Hays Program. Present address: Department of Physiology, University of Zagreb, Faculty ofOperated by the Union Carbide Corporation for the Department of Energy.     

The early response of59Fe incorporation in the bone marrow of irradiated rats

Summary The change in radioiron uptake in selected bone marrow samples in irradiated rats is representative of the total skeletal uptake only if the baseline or radioresistant uptake has been subtracted.This paper is based on work performed under contract with the US Energy Research and Development Administration at the University of Rochester Biomedical and Environmental Research Project, and has been assigned Report No. UR-3490-949.     

Alterations in bone-marrow cellularity following thymectomy in rats.

The number of nucleated marrow cells was decreased following neonatal thymectomy in rats, and was corrected by administration of syngeneic lymphoid cells, or by implantation of a syngeneic testis. These results suggest that, in the rat, as has been shown previously in the mouse, lymphoid cells exert parital control over bone marrow cellularity and this effect may be further modulated by sex steroids.     

Cure of osteopetrosis by allogenic bone marrow injection in the double mutant "osteopetrosi-athymic" rat]

The cure of osteopetrosis by allogenic bone marrow injection has been obtained in homozygous rats for both mutations, osteopetrosis (op) and athymic nude (rnu). This new animal model will help in studying the eventual relationship between the bone resorption process and the immunological reconstitution.     

Alterations in bone-marrow cellularity following thymectomy in rats

Summary The number of nucleated marrow cells was decreased following neonatal thymectomy in rats, and was corrected by administration of syngeneic lymphoid cells, or by implantation of a syngeneic testis. These results suggest that, in the rat, as has been shown previously in the mouse, lymphoid cells exert parital control over bone marrow cellularity and this effect may be further modulated by sex steroids.Supported in part by NSF-RIAS 77-06922, NIH AM21137 and the Morseman Foundation.     

Immune T cells controlTrypanosoma cruzi infections

Summary Immune but not normal T cells were able fully to restore the ability of thymectomized, irradiated, fetal liver reconstituted B mice to controlTrypanosoma cruzi infections.We are indebed to Dr. A.F. Pestana de Castro for his suggestions.     

Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice

Bone marrow stroma produces positive and negative growth regulators which constitute the hematopoietic microenvironment. As many tumors metastasize to the bones, these regulators may also influence tumor growth. Hematopoietic cytokines may indeed exert both positive and negative effect on tumor growth. We report that, when mixed with tumor cells. adherent bone marrow cells inhibit primary tumor growth and metastases formation in mice transplanted with Lewis lung carcinoma or B16 melanoma. Peritoneal macrophages or lymph node cells did not exert any influence. The tumor inhibition was apparently due to soluble factor(s) released by marrow stromal cells. In cocultures with B16 melanoma cells, adherent bone marrow cells exerted a significant antiproliferative effect which was increased by previous culture of the bone marrow cells with granulocyte-macrophage colony-stimulating factor but not with macrophage colony-stimulating factor. Neither neutralizing antibodies against tumor necrosis factor-alpha, transforming growth factor-beta or interferon alpha/beta nor addition of Escherichia coli lipopolysaccharide to generate inflammatory cytokines could affect the antiproliferative effect of bone marrow stromal cells. The bone marrow stroma factor(s) which inhibit tumor growth might, therefore, be a novel growth regulator.     

Glykogenbildung nach Thymektomie

Summary (1) No differences were found in the glycogen contents in liver, heart, and various other muscles between thymectomized and normal rats.(2) There are likewise no differences in glycogen synthesis in the diaphragm in the presence of glucose, alone and with insulin, between thymectomized and normal rats.(3) The weight of adrenal glands, absolute as well as in relation to the body-weight, shows no difference too between thymectomized and normal rats.     

Acceleration of muscle regeneration by bone marrow cells

Summary Myogenesis was accelerated by addition of bone marrow cells to muscle minces cultures in diffusion chambers. This effect was inhibited by using gold suppressed bone Marrow cells.Acknowledgment. We thank Dr Z. Ben-Ishay and Mrs S. Sharon for the help with the preparation of the chambers and the bone marrow suspensions.     

Cell proliferation in the bone marrow and thymus following partial bone marrow aspiration

Summary Aspiration of the one femoral bone marrow caused a significant rise of the cell population, arrested in colchicine-metaphase both of the bone marrow from the other femur and of the thymus.     

Collagen synthesis by human bone marrow fibroblasts

Collagen synthesis was measured in fibroblast cultures derived from normal and acute lymphoblastic leukemia (ALL) bone marrow. Collagen production was higher in normal than in ALL fibroblasts. These cells elaborate type I and type III procollagens in a ratio that depends on cell density and whether cells originate from normal or ALL bone marrow.     

The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity

The number of mature osteoblasts and marrow adipocytes in bone is influenced by the differentiation of the common mesenchymal progenitor cell towards one phenotype and away from the other. Consequently, factors which promote adipogenesis not only lead to fatty marrow but also inhibit osteoblastogenesis, resulting in decreased osteoblast numbers, diminished bone formation and, potentially, inadequate bone mass and osteoporosis. In addition to osteoblast and bone adipocyte numbers being influenced by this skewing of progenitor cell differentiation towards one phenotype, mature osteoblasts and adipocytes secrete factors which may evoke changes in the cell fate and function of each other. This review examines the endogenous factors, such as PPAR-γ2, Wnt, IGF-1, GH, FGF-2, oestrogen, the GP130 signalling cytokines, vitamin D and glucocorticoids, which regulate the selection between osteoblastogenesis and adipogenesis and the interrelationship between fat and bone. The role of adipokines on bone, such as adiponectin and leptin, as well as adipose-derived oestrogen, is reviewed and the role of bone as an energy regulating endocrine organ is discussed.     

Haemopoietic stem cell concentration and CFUs in DNA synthesis in bone marrow from different bone regions

Summary The concentration of colony-forming cells (CFUs) is about 40% less in sternal marrow than in the marrow of lumbar vertebrae and femora. Marrow of trabecular bones in lumbar vertebrae contains fewer mitotically active CFUs than marrow of trabecular bones in the femoral distal epiphysis and metaphysis, or the peripheral marrow near the cortical bone in the femoral diaphysis. Only a minor part of the variability of the results in the CFU-assay is due to differences in CFU-concentrations between individual donor mice; pooling of the cell suspensions does not substantially decrease variability. Specific pathogen-free mice yield the same results as BALB/c mice from conventional breeding.Acknowledgments. This work was performed with support of Euratom contract No. 233-771 BIO B. We thank L. Tessens for his excellent technical assistance.     

Regulation of neutrophil trafficking from the bone marrow

Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation. This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed.     

Influence of the thymus hormone on radioleucosis in mice]

A partially purified thymic extract has determined the development of leucosis in 10 thymectomized irradiated CC57Bl mice out of 25. The pure hormone isolated from the same extract prevented the development of leucosis in intact irradiated Mice. This seems to indicate the presence of a second active substance in the extract (enhancing the development of the leucosis).