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Sample records for bone marrow progenitor

  1. Increased FDG bone marrow uptake after intracoronary progenitor cell therapy

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    Doebert, N.; Menzel, C.; Diehl, M.; Hamscho, N.; Zaplatnikov, K.; Gruenwald, F. [Dept. of Nuclear Medicine, Univ. of Frankfurt (Germany)

    2005-02-01

    Patients with coronary artery disease who undergo FDG PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. Aim of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. Patients, methods: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3{+-}2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10{+-}1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. Results: In patients (n=70) who received PCT without G-CSF, BMU media (1.3) was slightly, but significantly higher than in the controls (1.0) (p=0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p=0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p=0.023). Leucocyte blood levels were significantly higher in patients with a BMU {>=}2.5 compared to patients with a bone marrow SUVmax<2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p=0.38). Conclusion: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplitifcation of BMU. (orig.)

  2. Characterization of vascular endothelial progenitor cells from chicken bone marrow

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    Bai Chunyu

    2012-05-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC are a type of stem cell used in the treatment of atherosclerosis, vascular injury and regeneration. At present, most of the EPCs studied are from human and mouse, whereas the study of poultry-derived EPCs has rarely been reported. In the present study, chicken bone marrow-derived EPCs were isolated and studied at the cellular level using immunofluorescence and RT-PCR. Results We found that the majority of chicken EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P 1, -5 and -9 were typically “S”-shaped. The viability of chicken EPCs, before and after cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1 uptake assays and immunofluorescent detection of the cell surface markers CD34, CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation of endothelial-specific Weibel-Palade bodies using transmission electron microscopy further confirmed that the cells were of endothelial lineage. In addition, chicken EPCs differentiated into endothelial cells and smooth muscle cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the chicken EPCs retained multipotency in vitro. Conclusions These results suggest that chicken EPCs not only have strong self-renewal capacity, but also the potential to differentiate into endothelial and smooth muscle cells. This research provides theoretical basis and experimental evidence for potential therapeutic application of endothelial progenitor cells in the treatment of atherosclerosis, vascular injury and diabetic complications.

  3. Bone marrow endothelial progenitors in atherosclerotic plaque resolution

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    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

    2013-01-01

    Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

  4. Global transcriptome analysis of T-competent progenitors in the bone marrow

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    Vionnie W.C. Yu

    2015-09-01

    Full Text Available T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015 [1]. Selective endogenous depletion of Ocn+ cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR led to reduction of T-competent common lymphoid progenitors (Ly6D− CLPs in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn+ cells in the bone marrow ensures the production of Ly6D− CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D− CLPs derived from Ocn+ cells deleted mice (OcnCre+;iDTR compared to those derived from control littermates (OcnCre−;iDTR. These data are publically available from NCBI Gene Expression Omnibus (GEO with the accession number GSE66102.

  5. In vitro studies on the radiosensitivity of multipotent hemopoietic progenitors in canine bone marrow

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    Kreja, L.; Weinsheimer, W.; Nothdurft, W.

    1991-01-01

    The in vitro radiation response to 280-kV x-rays (does rate 72 cGy/min) of multipotent hemopoietic progenitor cells, mixed colony-forming units (CFU-mix), from canine bone marrow was assayed and compared to the radiation response characteristics of early erythroid progenitors, erythroid burst-forming units (BFU-E). To improve the colony-forming efficiency, the effect of various bone marrow cell separation techniques on colony formation of both progenitors was examined. The separation of bone marrow aspirates by discontinuous buoyant gradient centrifugation using the lymphocyte separation medium Lymphoprep with a density of 1.070 g/ml allowed the establishment of reproducible survival curves. The survival curves for both progenitors were strictly exponential, and CFU-mix were found to be more radiosensitive (D0 = 12 ± 2 cGy) than BFU-E (D0 = 16 ± 2 cGy)

  6. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

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    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  7. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

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    Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

    2013-01-01

    Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  8. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

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    Peter E Westerweel

    Full Text Available Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment.Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed.In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro.EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  9. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

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    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  10. Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice.

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    Maridas, David E; Rendina-Ruedy, Elizabeth; Le, Phuong T; Rosen, Clifford J

    2018-01-06

    Bone marrow stromal cells (BMSCs) constitute a cell population routinely used as a representation of mesenchymal stem cells in vitro. They reside within the bone marrow cavity alongside hematopoietic stem cells (HSCs), which can give rise to red blood cells, immune progenitors, and osteoclasts. Thus, extractions of cell populations from the bone marrow results in a very heterogeneous mix of various cell populations, which can present challenges in experimental design and confound data interpretation. Several isolation and culture techniques have been developed in laboratories in order to obtain more or less homogeneous populations of BMSCs and HSCs invitro. Here, we present two methods for isolation of BMSCs and HSCs from mouse long bones: one method that yields a mixed population of BMSCs and HSCs and one method that attempts to separate the two cell populations based on adherence. Both methods provide cells suitable for osteogenic and adipogenic differentiation experiments as well as functional assays.

  11. Bone marrow niche-inspired, multi-phase expansion of megakaryocytic progenitors with high polyploidization potential

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    Panuganti, Swapna; Papoutsakis, Eleftherios T.; Miller, William M.

    2010-01-01

    Background Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization, and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. Methods CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo), and all combinations of Interleukin (IL)-3, IL-6, IL-11, and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide to enhance polyploidization. Results Using Tpo+SCF+IL-3+IL-11, we obtained 3.5 CD34+CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2/pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. Nicotinamide more than doubled the percentage of high-ploidy Mks to 40%. Discussion We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed nicotinamide addition will greatly increase high-ploidy Mk production. PMID:20482285

  12. Bone marrow niche-inspired, multiphase expansion of megakaryocytic progenitors with high polyploidization potential.

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    Panuganti, Swapna; Papoutsakis, Eleftherios T; Miller, William M

    2010-10-01

    Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo) and all combinations of Interleukin (IL)-3, IL-6, IL-11 and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide (NIC) to enhance polyploidization. Using Tpo + SCF + IL-3 + IL-11, we obtained 3.5 CD34+ CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2 /pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. NIC more than doubled the percentage of high-ploidy Mks to 40%. We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed NIC addition will greatly increase high-ploidy Mk production.

  13. Interleukin-3 Does Not Affect the Differentiation of Mast Cells Derived from Human Bone Marrow Progenitors

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    Shimizu, Yuji; Matsumoto, Kenji; Okayama, Yoshimichi; Kentaro, Sakai; Maeno, Toshitaka; Suga, Tatsuo; Miura, Toru; Takai, Shinji; Kurabayashi, Masahiko; Saito, Hirohisa

    2008-01-01

    Although IL-3 is commonly used for culture of human progenitor-derived mast cells together with Stem cell factor (SCF) and IL-6, the effect of IL-3 on human mast cell differentiation has not been well elucidated. Human bone marrow CD34+ progenitors were cultured for up to 12 weeks in the presence of rhSCF and rhIL-6 either with rhIL-3 (IL-3 (+)) or without rhIL-3 (IL-3 (−)) for the initial 1-week of culture. Total cell number increased at 2 weeks in IL-3 (+), as compared to IL-3 (−), but changes in the appearance of mast cells were delayed. When IL-3 was present for the initial 1-week culture, granules looked more mature with IL-3 than without IL-3. However, tryptase and chymase contents, and surface antigen expression (CD18, CD51, CD54, and CD117) were not altered by IL-3. Surface expression and mRNA level of FcεRIα and histamine release by crosslinking of FcεRIα did not differ from one preparation to the next. GeneChip analysis revealed that no significant differences were observed between IL-3 (+) and IL-3 (−) cells either when inactivated or activated by aggregation of FcεRIα. These findings indicate that initial incubation of human bone marrow CD34+ progenitors with IL-3 does not affect the differentiation of mast cells. PMID:18214796

  14. Bone marrow aspiration

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    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  15. Cigarette Smoking Is Associated with a Lower Concentration of CD105+ Bone Marrow Progenitor Cells

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    Shaul Beyth

    2015-01-01

    Full Text Available Cigarette smoking is associated with musculoskeletal degenerative disorders, delayed fracture healing, and nonunion. Bone marrow progenitor cells (BMPCs, known to express CD105, are important in local trophic and immunomodulatory activity and central to musculoskeletal healing/regeneration. We hypothesized that smoking is associated with lower levels of BMPC. Iliac bone marrow samples were collected from individuals aged 18–65 years during the first steps of pelvic surgery, under IRB approval with informed consent. Patients with active infectious or neoplastic disease, a history of cytotoxic or radiation therapy, primary or secondary metabolic bone disease, or bone marrow dysfunction were excluded. Separation process purity and the number of BMPCs recovered were assessed with FACS. BMPC populations in self-reported smokers and nonsmokers were compared using the two-tailed t-test. 13 smokers and 13 nonsmokers of comparable age and gender were included. The average concentration of BMPCs was 3.52 × 105/mL ± 2.45 × 105/mL for nonsmokers versus 1.31 × 105/mL ± 1.61 × 105/mL for smokers (t= 3.2, P=0.004. This suggests that cigarette smoking is linked to a significant decrease in the concentration of BMPCs, which may contribute to the reduced regenerative capacity of smokers, with implications for musculoskeletal maintenance and repair.

  16. HEMATOPOIETIC PROGENITOR CELL CONTENT OF VERTEBRAL BODY MARROW USED FOR COMBINED SOLID ORGAN AND BONE MARROW TRANSPLANTATION

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    Rybka, Witold B.; Fontes, Paulo A.; Rao, Abdul S.; Winkelstein, Alan; Ricordi, Camillo; Ball, Edward D.; Starzl, Thomas E.

    2010-01-01

    While cadaveric vertebral bodies (VB) have long been proposed as a suitable source of bone marrow (BM) for transplantation (BMT), they have rarely been used for this purpose. We have infused VB BM immediately following whole organ (WO) transplantation to augment donor cell chimerism. We quantified the hematopoietic progenitor cell (HPC) content of VB BM as well as BM obtained from the iliac crests (IC) of normal allogeneic donors (ALLO) and from patients with malignancy undergoing autologous marrow harvest (AUTO). Patients undergoing WOIBM transplantation also had AUTO BM harvested in the event that subsequent lymphohematopoietic reconstitution was required. Twenty-four VB BM, 24 IC BM-ALLO, 31 IC AUTO, and 24 IC WO-AUTO were harvested. VB BM was tested 12 to 72 hr after procurement and infused after completion ofWO grafting. IC BM was tested and then used or cryopreserved immediately. HPC were quantified by clonal assay measuring CFU-GM, BFU-E, and CFU-GEMM, and by flow cytometry for CD34+ progenitor cells. On an average, 9 VB were processed during each harvest, and despite an extended processing time the number of viable nucleated cells obtained was significantly higher than that from IC. Furthermore, by HPC content, VB BM was equivalent to IC BM, which is routinely used for BMT. We conclude that VB BM is a clinically valuable source of BM for allogeneic transplantation. PMID:7701582

  17. Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

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    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

    2012-01-01

    The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

  18. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

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    P. Alvarez

    2013-01-01

    Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  19. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

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    Otsuru, Satoru; Tamai, Katsuto; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-01-01

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood

  20. Radiation-induced enlargement of granulocytic and macrophage progenitor cells in mouse bone marrow

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    Metcalf, D; Johnson, G R; Wilson, J [Walter and Eliza Hall Inst. of Medical Research, Parkville (Australia)

    1977-01-01

    The peak sedimentation velocity of C/sub 57/BL mouse bone marrow progenitors of granulocytes and macrophages (GM-colony-forming cells, GM-CFC's) increased from 4.3 mm/h to 7 to 8 mm/h by 2 days after 250 rad whole body irradiation and slowly returned to normal over the next 3 weeks. Preliminary irradiation and/or endotoxin injection did not prevent this radiation-induced change. Some change in sedimentation velocity was seen with as little as 100 rad irradiation. Neither buoyant density nor cell cycle changes could account for the sedimentation velocity data which therefore indicate a major volume increase in the GM-CFC's. This size enlargement affected all subpopulations of GM-CFC's which consequently maintained their size relationship with one another.

  1. Subsequent donation requests among 2472 unrelated hematopoietic progenitor cell donors are associated with bone marrow harvest

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    Lown, Robert N.; Tulpule, Sameer; Russell, Nigel H.; Craddock, Charles F.; Roest, Rochelle; Madrigal, J. Alejandro; Shaw, Bronwen E.

    2013-01-01

    Approximately 1 in 20 unrelated donors are asked to make a second donation of hematopoietic progenitor cells, the majority for the same patient. Anthony Nolan undertook a study of subsequent hematopoietic progenitor cell donations made by its donors from 2005 to 2011, with the aims of predicting those donors more likely to be called for a second donation, assessing rates of serious adverse reactions and examining harvest yields. This was not a study of factors predictive of second allografts. During the study period 2591 donations were made, of which 120 (4.6%) were subsequent donations. The median time between donations was 179 days (range, 21–4016). Indications for a second allogeneic transplant included primary graft failure (11.7%), secondary graft failure (53.2%), relapse (30.6%) and others (1.8%). On multivariate analysis, bone marrow harvest at first donation was associated with subsequent donation requests (odds ratio 2.00, P=0.001). The rate of serious adverse reactions in donors making a subsequent donation appeared greater than the rate in those making a first donation (relative risk=3.29, P=0.005). Harvest yields per kilogram recipient body weight were equivalent between donations, although females appeared to have a lower yield at the subsequent donation. Knowledge of these factors will help unrelated donor registries to counsel their donors. PMID:23812935

  2. Novel Vanadium-Loaded Ordered Collagen Scaffold Promotes Osteochondral Differentiation of Bone Marrow Progenitor Cells

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    Ana M. Cortizo

    2016-01-01

    Full Text Available Bone and cartilage regeneration can be improved by designing a functionalized biomaterial that includes bioactive drugs in a biocompatible and biodegradable scaffold. Based on our previous studies, we designed a vanadium-loaded collagen scaffold for osteochondral tissue engineering. Collagen-vanadium loaded scaffolds were characterized by SEM, FTIR, and permeability studies. Rat bone marrow progenitor cells were plated on collagen or vanadium-loaded membranes to evaluate differences in cell attachment, growth and osteogenic or chondrocytic differentiation. The potential cytotoxicity of the scaffolds was assessed by the MTT assay and by evaluation of morphological changes in cultured RAW 264.7 macrophages. Our results show that loading of VOAsc did not alter the grooved ordered structure of the collagen membrane although it increased membrane permeability, suggesting a more open structure. The VOAsc was released to the media, suggesting diffusion-controlled drug release. Vanadium-loaded membranes proved to be a better substratum than C0 for all evaluated aspects of BMPC biocompatibility (adhesion, growth, and osteoblastic and chondrocytic differentiation. In addition, there was no detectable effect of collagen or vanadium-loaded scaffolds on macrophage viability or cytotoxicity. Based on these findings, we have developed a new ordered collagen scaffold loaded with VOAsc that shows potential for osteochondral tissue engineering.

  3. Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

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    Jing Xia

    Full Text Available During retina development, retinal progenitor cell (RPC proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC self-renewal, as well as betacellulin (BTC, an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.

  4. In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

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    P.B. Soares

    2013-01-01

    Full Text Available Imatinib mesylate (IM is used to treat chronic myeloid leukemia (CML because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM. The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM, using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells increased. At higher concentrations (15 µM, the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control. Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

  5. A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

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    Richard Longeras

    2012-01-01

    Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

  6. Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

    Science.gov (United States)

    Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2017-12-01

    Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

  7. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

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    Li-Li Wang

    Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

  8. Role of bone marrow-derived stem cells, renal progenitor cells and ...

    African Journals Online (AJOL)

    It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Characterization of HSCs ...

  9. Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors

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    Pastor Maria

    2010-06-01

    Full Text Available Abstract Background Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats. Results Two mast cell specific antibodies, mAb AA4 and mAb BGD6, were used to distinguish the committed mast cell precursor from more mature mast cells. The peritoneal cavity was depleted of mast cells using distilled water. Twelve hours after distilled water injection, very immature mast cells could be isolated from the blood and by 48 hours were present in the peritoneal cavity. At this same time the percentage of mast cells in mitosis increased fourfold. Mast cell depletion of the peritoneal cavity also reduced the total number of mast cells in the bone marrow, but increased the number of mast cell committed precursors. Conclusions In response to mast cell depletion of the peritoneal cavity, a mast cell progenitor is released into the circulation and participates in repopulation of the peritoneal cavity, while the committed mast cell precursor is retained in the bone marrow.

  10. Progenitor cells of erythroblasts: an in vitro investigation of erythropoietin-responsive cells of guinea pig bone marrow

    International Nuclear Information System (INIS)

    Rosse, C.; Beaufait, D.W.

    1978-01-01

    The experiments were designed to therst whether erythroblast progenitor cell function could be demonstrated in a morphological cell type designated as transitional cells. Two cell fractions were obtained from the bone marrow of normal and polycythemic guinea pigs. One fraction (F1) was enriched in transitional cells and contained few other cell types which could be considered as candidates for erythropoietin responsive cells (ERC). The other fraction (F2) contained undifferentiated blast cells as well as transitional cells. The effect of human urinary erythropoiesis stimulating factors (ESF) on heme synthesis was compared in these two fractions by measuring 59 Fe incorporation into heme. ESF was more effective in stimulating heme synthesis in guinea pig bone marrow cells than homologous sera obtained from anemic or hypoxic animals. The majority of ERC sedimented in F2, but the stimulation index was comparable in the two fractions. It was confirmed by radioautography that the ESF response in F1 was due to the generation of proerythroblasts and basophilic erythroblasts that incorporated 55 Fe. The generation of these cells in F1 was dependent on the addition of ESF to the cultures, whereas 55 Fe-labeled erythroblasts were recovered from cultures of F2 not supplemented with ESF. ESF induced a proportion of transitional cells to incorporate 55 Fe in both F1 and F2. Transitional cells were the only cell type in which heme synthesis was dependent on ESF. Radioautography with 55 Fe identified a proportion of these cells as ERC in both F1 and F2 fractions of bone marrow obtained from normal and polycythemic guinea pigs. The present studies show that some transitional cells function as progenitors of erythroblasts because they respond to ESF by initiation of heme synthesis and by transformation into the earliest recognizable erythroid cells

  11. Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

    Science.gov (United States)

    Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

    2012-06-01

    We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

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    Sara Rocío Chuguransky

    2016-01-01

    Full Text Available Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs that impair bone marrow progenitor cell (BMPC osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization and chondrogenesis (glycosaminoglycan production of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b increased bone marrow adiposity; and (c deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis. Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.

  13. [Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

    Science.gov (United States)

    Tanabe, Y; Dan, K; Kuriya, S; Nomura, T

    1989-10-01

    The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

  14. Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

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    Dong-Mei Jiang

    Full Text Available BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH. Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2 expression, prostacyclin (PGI2 and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

  15. Autologous bone marrow concentrate enriched in progenitor cells — An adjuvant in the treatment of acute myocardial infarction

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    Vinay Sanghi

    2016-06-01

    Full Text Available Despite advances in revascularization techniques, acute myocardial infarction (AMI still carries significant morbidity and mortality. Over the past decade, the use of regenerative medicine methodologies, and specifically bone marrow derived progenitor cell therapy has been tested in more than 35 Phase I and Phase II clinical studies demonstrating overall safety and measurable clinical benefit, 12–61 months post-treatment as evaluated by improvement in the Left Ventricular Ejection Fraction (LVEF and changes in infarct size post AMI. Recent meta-analysis on the subject highlighted several important parameters that include timing of the cell therapy post AMI, the cell dose, and the baseline LVEF on enrollment. We further postulate that the mythologies and timing for cell handling and delivery including the specific devices are essential for clinical efficacy. Addressing this we have developed a rapid 60 to 90 minute process and integrated system which is carried out in the heart catheter lab, using a combination product (U.S. Food and Drug broadly defined as the combination of co-labeled optimized “cell friendly” devices, effective cell/biological formulation and dose for harvesting, processing, verifying, and delivering an autologous dose of bone marrow progenitor/stem cells via the intracoronary artery proximal to the infarct myocardial region. The methodology has been demonstrated to be safe and feasible for autologous in vivo use and presented by our groups' earlier studies1–3 and most recently used in a Phase Ib critical limb ischemia trial of 17 subjects (NCT01472289 (manuscript under preparation. This is the first case study prior to beginning the AMIRST trial [Acute Myocardial Infarction Rapid Stem cell Therapy], specific to our proprietary combination product kit for acute myocardial infarction, and was completed under the Independent Ethics Committee and Institutional Committee for Stem Cell Research and Therapy approval (TIEC

  16. In vitro analysis of age-related changes in the developmental potential of bone marrow thymocyte progenitors.

    Science.gov (United States)

    Sharp, A; Kukulansky, T; Globerson, A

    1990-12-01

    Mechanisms underlying the age-related decrease in the developmental capacity of thymocyte progenitors from the bone marrow (BM) were analyzed, focussing on interaction of these cells with the thymic microenvironment. We employed the experimental model in which mixtures of young and old mouse BM cells, congenic for the Thy-1 marker, were seeded onto fetal thymus (FT) explains depleted of self lymphocytes and the levels of Thy-1+ cells developing from each of the two donor types were measured. When cells from young and old BM donors were seeded simultaneously, in saturating quantities, a higher level of T cells developed from the young donors. To find out whether there were originally more thymocyte progenitors in the young BM, we carried out the competitive colonization under limiting dilution conditions and found that the advantage of the young had diminished under these conditions, thus suggesting that the age-related changes could not be related solely to quantitative differences. We then incubated the FT sequentially with old donor cells for 24 h, followed by young for an additional 48 h and found that the advantage of the young progenitors was eliminated. We thus established that the initial stage of colonization of the FT was important in determining the outcome of the subsequent development. The kinetics of simultaneous competition within the FT, however, revealed that the advantage of the young BM-derived cells became significant only from day 7 in organ culture, thus suggesting that sequential divisions of these cells were at a higher level than those of the old. Recolonization of FT explants by young or old BM-derived thymocytes obtained from the first colonization of the FT stroma showed a reduced, but still significant advantage for the young BM-derived cells over the old. Thus, we concluded that the old BM thymocyte progenitors manifested a qualitative disadvantage which became apparent during competitive colonization of the FT.

  17. Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

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    Fabian Duttenhoefer

    2015-01-01

    Full Text Available In bone tissue engineering (TE endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs are a rich source of mesenchymal stem cells (MSCs able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+ were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+ or medium containing platelet lysate (PL. MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

  18. Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

    Directory of Open Access Journals (Sweden)

    Pascariello Caterina

    2008-05-01

    Full Text Available Abstract Background Aldehyde dehydrogenase (ALDH is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007. The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively. As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a. Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA. Conclusion Our study, comparing surface antigen expression of

  19. Stromal and Hematopoietic Progenitors from C57/BI/6N Murine Bone Marrow After 30-Day "BION-M1" Spaceflight.

    Science.gov (United States)

    Markina, Elena; Andreeva, Elena; Andrianova, Irina; Sotnezova, Elena; Buravkova, Ludmila

    2018-05-02

    Elucidation of the spaceflight (SF) effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this was provided by project "BION-M1". The purpose of this study was to evaluate the effects of 30-day SF on biosatellite, 7-day recovery (SFR), and subsequent ground control (GC) experiment on the mononuclear cells (MNCs) from C57/BI/6N murine tibia bone marrow. Also, hematopoietic and stromal precursor functions were characterized ex vivo. There was no significant difference in the total MNC number between experimental groups. After SF, immunophenotyping revealed an increase of large-sized CD45 + MNCs corresponded to committed hematopoietic progenitors. The total hematopoietic colony-forming unit (CFU) number decreased after SF and did not restore after 7 day of recovery due to predominant reduction of bi- and multipotent CFUs and primitive burst-forming units in favor of unipotent CFUs. Functional activity of stromal precursors in vitro was only slightly altered. SF cells displayed the enhanced expression of alkaline phosphatase. The data of the GC experiment demonstrated the preservation of the functional activity of progenitor cells from mice bone marrow. The activation of erythropoiesis in expense of burst-forming units of erythrocytes elevation was detected. After 7 days of recovery, the number of colony-forming units of fibroblast (CFUs-f) was similar to the vivarium control, while the proliferative activity of bone marrow stromal precursors decreased. The present study demonstrated that certain hematopoietic progenitors are susceptible to SF factors, while the stromal precursors displayed a certain degree of resistance. These data indicate mild and reversible alterations of bone marrow progenitors after SF.

  20. Effects of hematopoietic growth factors on purified bone marrow progenitor cells

    NARCIS (Netherlands)

    F.J. Bot (Freek)

    1992-01-01

    textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3

  1. Rat bone marrow progenitor cells transduced in situ by rSV40 vectors differentiate into multiple central nervous system cell lineages.

    Science.gov (United States)

    Louboutin, Jean-Pierre; Liu, Bianling; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

    2006-12-01

    Using bone marrow-directed gene transfer, we tested whether bone marrow-derived cells may function as progenitors of central nervous system (CNS) cells in adult animals. SV40-derived gene delivery vectors were injected directly into femoral bone marrow, and we examined transgene expression in blood and brain for 0-16 months thereafter by immunostaining for FLAG epitope marker. An average of 5% of peripheral blood cells and 25% of femoral marrow cells were FLAG(+) throughout the study. CNS FLAG-expressing cells were mainly detected in the dentate gyrus (DG) and periventricular subependymal zone (PSZ). Although absent before 1 month and rare at 4 months, DG and PSZ FLAG(+) cells were abundant 16 months after bone marrow injection. Approximately 5% of DG cells expressed FLAG, including neurons (48.6%) and microglia (49.7%), and occasional astrocytes (1.6%), as determined by double immunostaining for FLAG and lineage markers. These data suggest that one or more populations of cells resident within adult bone marrow can migrate to the brain and differentiate into CNS-specific cells.

  2. G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells.

    Science.gov (United States)

    Brunner, Stefan; Huber, Bruno C; Fischer, Rebekka; Groebner, Michael; Hacker, Marcus; David, Robert; Zaruba, Marc-Michael; Vallaster, Marcus; Rischpler, Christoph; Wilke, Andrea; Gerbitz, Armin; Franz, Wolfgang-Michael

    2008-06-01

    Besides its classical function in the field of autologous and allogenic stem cell transplantation, granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI) by mobilization of bone marrow-derived progenitor cells (BMCs) and in addition by activation of multiple signaling pathways. In the present study, we focused on the impact of G-CSF on migration of BMCs and the impact on resident cardiac cells after MI. Mice (C57BL/6J) were sublethally irradiated, and BM from green fluorescent protein (GFP)-transgenic mice was transplanted. Coronary artery ligation was performed 10 weeks later. G-CSF (100 microg/kg) was daily injected for 6 days. Subpopulations of enhanced GFP(+) cells in peripheral blood, bone marrow, and heart were characterized by flow cytometry. Growth factor expression in the heart was analyzed by quantitative real-time polymerase chain reaction. Perfusion was investigated in vivo by gated single photon emission computed tomography (SPECT). G-CSF-treated animals revealed a reduced migration of c-kit(+) and CXCR-4(+) BMCs associated with decreased expression levels of the corresponding growth factors, namely stem cell factor and stromal-derived factor-1 alpha in ischemic myocardium. In contrast, the number of resident cardiac Sca-1(+) cells was significantly increased. However, SPECT-perfusion showed no differences in infarct size between G-CSF-treated and control animals 6 days after MI. Our study shows that G-CSF treatment after MI reduces migration capacity of BMCs into ischemic tissue, but increases the number of resident cardiac cells. To optimize homing capacity a combination of G-CSF with other agents may optimize cytokine therapy after MI.

  3. Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

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    Hayam Abdel Meguid El Aggan

    2013-09-01

    Full Text Available Introduction: Chronic allograft nephropathy (CAN is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs and mesenchymal stem cells (MSCs. Characterization of HSCs includes their multipotency, expression of typical surface markers such as CD34 and CD45, while characterization of MSC includes their multipotency, expression of typical surface markers such as CD90 and CD105, and the absence of hemopoietic lineage markers. Aim & methods: The aim of the present work was to study the role of bone marrow-derived HSCs and MSCs, renal progenitor cells and SCF in chronic renal allograft nephropathy in relation to renal hemodynamics and histopathological changes. We studied 30 patients with kidney transplantation for more than 6 months, divided into 15 patients with stable serum creatinine and 15 patients who developed CAN. Detection of HSCs and MSCs in the peripheral blood using flow cytometry via detection of CD34, CD45, CD117 and CD106, as well as immunohistochemical detection of CD34, CD133, VEGF and αSMA in transplanted kidney biopsies of patients with CAN were done. Results: There was a significant increase in the levels of SCF, number of peripheral blood HSCs and MSCs in both transplanted patient groups than the controls and they were higher in patients of group Ia than patients of group Ib, (F = 39.73, P < 0.001, (F = 13.28, P < 0.001, (F = 11.94, P < 0.001, respectively and this was accompanied by evident expression of markers of renal repair. Conclusion: Stem cells might have a role in renal regeneration in CAN and this may pave the way toward the use of stem cells in correction of CAN. KEYWORDS

  4. Human bone marrow mesenchymal progenitors: perspectives on an optimized in vitro manipulation

    Directory of Open Access Journals (Sweden)

    Eric Cordeiro-Spinetti

    2014-03-01

    Full Text Available When it comes to regenerative medicine, mesenchymal stem cells (MSCs are considered one of the most promising cell types for use in many cell therapies and bioengineering protocols. The International Society of Cellular Therapy recommended minimal criteria for defining multipotential MSC is based on adhesion and multipotency in vitro, and the presence or absence of select surface markers. Though these criteria help minimize discrepancies and allow some comparisons of data generated in different laboratories, the conditions in which cells are isolated and expanded are often not considered. Herein, we propose and recommend a few procedures to be followed to facilitate the establishment of quality control standards when working with mesenchymal progenitors isolation and expansion. Following these procedures, the classic Colony-Forming Unit-Fibroblast (CFU-f assay is revisited and three major topics are considered to define conditions and to assist on protocol optimization and data interpretation. We envision that the creation of a guideline will help in the identification and isolation of long-term stem cells and short-term progenitors to better explore their regenerative potential for multiple therapeutic purposes.

  5. Engraftment of Bone Marrow Progenitor Cells in a Rat Model of Asbestos-Induced Pulmonary Fibrosis

    OpenAIRE

    Spees, Jeffrey L.; Pociask, Derek A.; Sullivan, Deborah E.; Whitney, Mandolin J.; Lasky, Joseph A.; Prockop, Darwin J.; Brody, Arnold R.

    2007-01-01

    Rationale: Bone marrow–derived cells have been shown to engraft during lung fibrosis. However, it is not known if similar cells engraft consequent to inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells proliferate and differentiate at sites of injury.

  6. Bone Marrow Diseases

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  7. Immune-mediated bone marrow failure syndromes of progenitor and stem cells: molecular analysis of cytotoxic T cell clones.

    Directory of Open Access Journals (Sweden)

    Ramon Tiu

    2007-03-01

    Full Text Available The unique structure of the T cell receptor (TCR enables molecular identification of individual T cell clones and provides an unique opportunity for the design of molecular diagnostic tests based on the structure of the rearranged TCR chain e.g., using the TCR CDR3 region. Initially, clonal T cell malignancies, including T cell large granular lymphocyte leukemia (T-LGL, mucosis fungoides and peripheral T cell lymphoma were targets for the TCR-based analytic assays such as detection of clonality by T-gamma rearrangement using y-chain-specific PCR or Southern Blotting. Study of these disorders facilitated further analytic concepts and application of rational methods of TCR analysis to investigations of polyclonal T cell-mediated diseases. In hematology, such conditions include graft versus host disease (GvHD and immune-mediated bone marrow failure syndromes. In aplastic anemia (AA, myelodysplastic syndrome (MDS or paroxysmal nocturnal hemoglobinuria (PNH, cytotoxic T cell responses may be directed against certain antigens located on stem or more lineage-restricted progenitor cells in single lineage cytopenias. The nature of the antigenic targets driving polyclonal CTL responses remains unclear. Novel methods of TCR repertoire analysis, include VB flow cytometry, peptide-specific tetramer staining, in vitro stimulation assays and TCR CDR3-specific PCR. Such PCR assay can be either VB family-specific or multiplexed for all VB families. Amplified products can be characterized and quantitated to facilitate detection of the most immunodominant clonotypes. Such clonotypes may serve as markers for the global polyclonal T cell response. Identification of these clonotypes can be performed in blood and tissue biopsy material by various methods. Once immunodominant clonotypes corresponding to pathogenic CTL clones are identified they can serve as surrogate markers for the activity of the pathophysiologic process or even indicate the presence of specific

  8. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    International Nuclear Information System (INIS)

    Colnot, C.; Huang, S.; Helms, J.

    2006-01-01

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis

  9. Blood and Bone Marrow Transplant?

    Science.gov (United States)

    ... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

  10. Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

    OpenAIRE

    Hayam Abdel Meguid El Aggan; Mona Abdel Kader Salem; Nahla Mohamed Gamal Farahat; Ahmad Fathy El-Koraie; Ghaly Abd Al-Rahim Mohammed Kotb

    2013-01-01

    Introduction: Chronic allograft nephropathy (CAN) is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Char...

  11. High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

    Science.gov (United States)

    Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

    2009-07-15

    Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors

  12. Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Chenxi [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Chen, Mouying [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); You, Huihui [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Qiu, Feng [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Wen, Huaxiao; Yuan, Junlin [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Xiang, Shuanglin, E-mail: xshlin@hunnu.edu.cn [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Yang, Xu, E-mail: yangxu@mail.ccnu.edu.cn [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China)

    2017-06-01

    Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m{sup 3} FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of

  13. Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

    International Nuclear Information System (INIS)

    Wei, Chenxi; Chen, Mouying; You, Huihui; Qiu, Feng; Wen, Huaxiao; Yuan, Junlin; Xiang, Shuanglin; Yang, Xu

    2017-01-01

    Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m 3 FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of GM

  14. Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

    Science.gov (United States)

    Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

    2018-03-01

    Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences

  15. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia.

    NARCIS (Netherlands)

    Schrezenmeier, H.; Passweg, J.R.; Marsh, J.C.; Bacigalupo, A.; Bredeson, C.N.; Bullorsky, E.; Camitta, B.M.; Champlin, R.E.; Gale, R.P.; Fuhrer, M.; Klein, J.P.; Locasciulli, A.; Oneto, R.; Schattenberg, A.V.M.B.; Socie, G.; Eapen, M.

    2007-01-01

    We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic

  16. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

    Directory of Open Access Journals (Sweden)

    Bikul Das

    2008-10-01

    Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

  17. Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.

    Science.gov (United States)

    Xu, Wen Wen; Li, Bin; Guan, Xin Yuan; Chung, Sookja K; Wang, Yang; Yip, Yim Ling; Law, Simon Y K; Chan, Kin Tak; Lee, Nikki P Y; Chan, Kwok Wah; Xu, Li Yan; Li, En Min; Tsao, Sai Wah; He, Qing-Yu; Cheung, Annie L M

    2017-02-10

    Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

  18. Bone marrow transplant

    Science.gov (United States)

    ... Arrange medical leave from work Take care of bank or financial statements Arrange care of pets Arrange ... Bleeding during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Central venous catheter - flushing ...

  19. Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis

    International Nuclear Information System (INIS)

    Aguirre, A.; Planell, J.A.; Engel, E.

    2010-01-01

    Research highlights: → BM-EPCs and MSCs establish complex, self-organizing structures in co-culture. → Co-culture decreases proliferation by cellular self-regulatory mechanisms. → Co-cultured cells present an activated proangiogenic phenotype. → qRT-PCR and cluster analysis identify new target genes playing important roles. -- Abstract: Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3 days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response.

  20. Pre-irradiation of tissue culture flasks leads to diminished stem and progenitor cell production in long-term bone marrow cultures

    International Nuclear Information System (INIS)

    Rooney, P.; Wright, E.G.

    1993-01-01

    Empty plastic tissue culture flasks were exposed to X-irradiation doses of 0.3-10.0 Gy, prior to the establishment of long-term bone marrow cultures. During the course of a 10 week culture period, all irradiated plastic flasks exhibited a dramatic decrease in the number of both haemopoietic stem cells and myeloid progenitor cells, in the non-adherent layer, when compared with controls. This decrease was not due to a decrease in the number of non-adherent cells produced. Histological examination of non-adherent cells showed an increase in mature granulocytic cells with few blast cells. Morphologically, the adherent layers of irradiated flasks demonstrated a delay in appearance or absence of fat cell production. X-irradiation of glass tissue culture flasks had no deleterious effect. (author)

  1. Bone - marrow postirradiation syndrome

    International Nuclear Information System (INIS)

    Sesztakova, E.; Bilek, J.; Benova, K.; Novakova, J.; Culenova, K.

    2006-01-01

    Quantitative and qualitative changes in haemopoietic cells in chicken bone Marrow were investigated after acute single irradiation with doses 4.5 Gy and 5 Gy. Samples of bone marrow were obtained from proximal femoral epiphysis of decapitated chickens. Marrow smears were prepared and stained according to Pappenheim. Qualitative examination of myelogram showed proliferation of adipose tissue, hypocellularity, caryolyosis, caryorexis, disintegration of cells and proliferation of cells which could not be differentiated. Quantitative examination revealed high radiosensitivity of blast cells and lymphocytes shortly after irradiation. (authors)

  2. FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

    International Nuclear Information System (INIS)

    Ishino, Ruri; Minami, Kaori; Tanaka, Satowa; Nagai, Mami; Matsui, Keiji; Hasegawa, Natsumi; Roeder, Robert G.; Asano, Shigetaka; Ito, Mitsuhiro

    2013-01-01

    Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1 +/+ MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1 −/− MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1 +/+ and Med1 −/− MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells

  3. FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Ruri; Minami, Kaori; Tanaka, Satowa [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Nagai, Mami [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Matsui, Keiji; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Asano, Shigetaka [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan)

    2013-10-11

    Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

  4. Bone marrow transplantation immunology

    International Nuclear Information System (INIS)

    Trentin, J.J.; Kiessling, R.; Wigzell, H.; Gallagher, M.T.; Datta, S.K.; Kulkarni, S.S.

    1977-01-01

    Tests were made to determine whether genetic resistance (GR) to bone marrow transplantation represents a natural lymphoma-leukemia defense mechanism, as follows: (C57 x AKR) F 1 hybrid mice show GR to C57 parental bone marrow cells, but not to AKR parental bone marrow cells (C3H x AKR) F 1 hybrids show no GR to bone marrow transplantation from either parental strain. However, transplantation of AKR lymphoma cells into lethally irradiated ''resistant'' (C57 x AKR) F 1 and ''nonresistant'' (C3H x AKR) F 1 hybrids produced lymphomatous spleen colonies in ''nonresistant'' hybrids but not in ''resistant'' hybrids. Thus ''resistant'' (C57 x AKR) F 1 hybrids can recognize and reject AKR lymphoma cells, but not normal AKR bone marrow cells. A normal biologic role of leukemia-lymphoma surveillance was postulated for genetic resistance to marrow transplantation, directed at antigens which, like TL, are expressed on normal hemopoietic cells of some strains, but only on leukemic cells of other strains

  5. Bone--bone marrow interactions

    International Nuclear Information System (INIS)

    Patt, H.M.

    1976-01-01

    Within medullary cavities, blood formation tends to be concentrated near bone surfaces and this raises interesting questions about hematopoietic consequences of radionuclide fixation in osseous tissue. Thus, it may be important, on the one hand, to consider the medullary radiation dose distribution as well as total marrow dose from bone-bound radioelements and, on the other, to inquire about possible hematopoietic implications of radiation damage to endosteal surfaces per se. The reasons for this are discussed

  6. Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

    Science.gov (United States)

    Lippross, Sebastian; Loibl, Markus; Hoppe, Sven; Meury, Thomas; Benneker, Lorin; Alini, Mauro; Verrier, Sophie

    2011-01-01

    Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred. In recent years tissue engineers increasingly looked at the process of vessel neoformation because of its major importance for successful cell grafting to replace damaged tissue. Up to now one of the greatest problems preventing a clinical application is the large scale of expansion that is required for such purpose. We established a method to effectively enhance the expansion of CD34(+) and CD133(+) cells by the use of platelet-released growth factors (PRGF) as a media supplement. PRGF were prepared from thrombocyte concentrates and used as a media supplement to iscove's modified dulbecco's media (IMDM). EPC were immunomagnetically separated from human bone morrow monocyte cells and cultured in IMDM + 10% fetal calf serum (FCS), IMDM + 5%, FCS + 5% PRGF and IMDM + 10% PRGF. We clearly demonstrate a statistically significant higher and faster cell proliferation rate at 7, 14, 21, and 28 days of culture when both PRGF and FCS were added to the medium as opposed to 10% FCS or 10% PRGF alone. The addition of 10% PRGF to IMDM in the absence of FCS leads to a growth arrest from day 14 on. In histochemical, immunocytochemical, and gene-expression analysis we showed that angiogenic and precursor markers of CD34(+) and CD133(+) cells are maintained during long-term culture. In summary, we established a protocol to boost the expansion of CD34(+) and CD133(+) cells. Thereby we provide a technical step towards the clinical application of autologous stem cell

  7. Bone marrow transplantation

    International Nuclear Information System (INIS)

    Storb, R.; Santos, G.W.

    1979-01-01

    Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation

  8. Adhesive and mechanical regulation of mesenchymal stem cell differentiation in human bone marrow and periosteum-derived progenitor cells

    Directory of Open Access Journals (Sweden)

    Jeroen Eyckmans

    2012-08-01

    It has previously been demonstrated that cell shape can influence commitment of human bone marrow-derived mesenchymal stem cells (hBMCs to adipogenic, osteogenic, chondrogenic, and other lineages. Human periosteum-derived cells (hPDCs exhibit multipotency similar to hBMCs, but hPDCs may offer enhanced potential for osteogenesis and chondrogenesis given their apparent endogenous role in bone and cartilage repair in vivo. Here, we examined whether hPDC differentiation is regulated by adhesive and mechanical cues comparable to that reported for hBMC differentiation. When cultured in the appropriate induction media, hPDCs at high cell seeding density demonstrated enhanced levels of adipogenic or chondrogenic markers as compared with hPDCs at low cell seeding density. Cell seeding density correlated inversely with projected area of cell spreading, and directly limiting cell spreading with micropatterned substrates promoted adipogenesis or chondrogenesis while substrates promoting cell spreading supported osteogenesis. Interestingly, cell seeding density influenced differentiation through both changes in cell shape and non-shape-mediated effects: density-dependent adipogenesis and chondrogenesis were regulated primarily by cell shape whereas non-shape effects strongly influenced osteogenic potential. Inhibition of cytoskeletal contractility by adding the Rho kinase inhibitor Y27632 further enhanced adipogenic differentiation and discouraged osteogenic differentiation of hPDCs. Together, our results suggest that multipotent lineage decisions of hPDCs are impacted by cell adhesive and mechanical cues, though to different extents than hBMCs. Thus, future studies of hPDCs and other primary stem cell populations with clinical potential should consider varying biophysical metrics for more thorough optimization of stem cell differentiation.

  9. Translation of cell therapy into clinical practice: validation of an application procedure for bone marrow progenitor cells and platelet rich plasma.

    Science.gov (United States)

    Nowotny, Joerg; Farack, Jana; Vater, Corina; Johnsen, Matthias; Gelinsky, Michael; Tonn, Torsten; Kasten, Philip

    2016-04-06

    Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells (BMSC) and platelet rich plasma (PRP). However, there is a lack of standardized application procedures for clinical use. Therefore, a technique in accordance with the guidelines for advanced therapies medical products of the European Medicine Agency was developed and established. In detail, a process for the isolation and formulation of autologous bone marrow cells (BMC) and PRP in a clinical setting was validated. To investigate the influence of storage time and temperature on gel formation and gel stability, different concentrations of BMC were stored with and without additional platelets, thrombin and fibrinogen and analyzed over a period of 28 days. In addition, cell vitality using a live-dead staining and migration ability of human mesenchymal stem cells (hMSC) in the gel clot was investigated. For an optimized stable gel clot, human BMC and PRP should be combined with 10% to 20% fibrinogen (9 mg/mL to 18 mg/mL) and 5% to 20% thrombin (25 I.E. to 100 I.E.). Both freshly prepared and stored cells for 1 to 7 days had a stable consistence over 28 days at 37°C. Different platelet concentrations did not influence gel clot formation. The ratio of living cells did not decrease significantly over the observation period of 5 days in the live-dead staining. The study identified an optimal gel texture for local application of BMC and PRP. Seeded hMSC could migrate therein and were able to survive to initiate a healing cascade.

  10. Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

    Science.gov (United States)

    Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

    2016-10-01

    Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Post-irradiation thymocyte regeneration after bone marrow transplantation

    International Nuclear Information System (INIS)

    Boersma, W.J.A.

    1981-01-01

    Bone marrow cells were separated according to buoyant density, velocity sedimentation and cell surface charge. Fractionated (C3H x AKR)F 1 bone marrow cells were transplanted into lethally-irradiated C3H recipients. In all fractions, the CFUs content and the capacity to restore the thymus cell population were determined. For all the physical parameters tested, thymocyte progenitor cells show the same distribution as CFUs. The relationship between number of thymocyte progenitor cells and number of CFUs is dependent on density. Bone marrow progenitors of PHA responsive cells are of low buoyant density and show a distribution which resembles the distribution of the progenitors of Thy 1 positive cells. After transplantation of large numbers of bone marrow cells into irradiated mice, no significant change in the CFUs content of the thymus was observed. (author)

  12. Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide

    International Nuclear Information System (INIS)

    Winton, E.F.; Colenda, K.W.

    1987-01-01

    The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors

  13. Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts

    Science.gov (United States)

    Wang, Qi; Clarkson, Christina; Graham, Melanie; Donahue, Robert; Hering, Bernhard J.; Verfaillie, Catherine M.; Bansal-Pakala, Pratima; O'Brien, Timothy D.

    2015-01-01

    Background Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported. Methods We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. Results and Conclusions Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable. PMID:24825538

  14. The ERK5 and ERK1/2 signaling pathways play opposing regulatory roles during chondrogenesis of adult human bone marrow-derived multipotent progenitor cells.

    Science.gov (United States)

    Bobick, Brent E; Matsche, Alexander I; Chen, Faye H; Tuan, Rocky S

    2010-07-01

    Adult human bone marrow-derived multipotent progenitor cells (MPCs) are able to differentiate into a variety of specialized cell types, including chondrocytes, and are considered a promising candidate cell source for use in cartilage tissue engineering. In this study, we examined the regulation of MPC chondrogenesis by mitogen-activated protein kinases in an attempt to better understand how to generate hyaline cartilage in the laboratory that more closely resembles native tissue. Specifically, we employed the high-density pellet culture model system to assess the roles of ERK5 and ERK1/2 pathway signaling in MPC chondrogenesis. Western blotting revealed that high levels of ERK5 phosphorylation correlate with low levels of MPC chondrogenesis and that as TGF-beta 3-enhanced MPC chondrogenesis proceeds, phospho-ERK5 levels steadily decline. Conversely, levels of phospho-ERK1/2 paralleled the progression of MPC chondrogenesis. siRNA-mediated knockdown of ERK5 pathway components MEK5 and ERK5 resulted in increased MPC pellet mRNA transcript levels of the cartilage-characteristic marker genes SOX9, COL2A1, AGC, L-SOX5, and SOX6, as well as enhanced accumulation of SOX9 protein, collagen type II protein, and Alcian blue-stainable proteoglycan. In contrast, knockdown of ERK1/2 pathway members MEK1 and ERK1 decreased expression of all chondrogenic markers tested. Finally, overexpression of MEK5 and ERK5 also depressed MPC chondrogenesis, as indicated by diminished activity of a co-transfected collagen II promoter-luciferase reporter construct. In conclusion, our results suggest a novel role for the ERK5 pathway as an important negative regulator of adult human MPC chondrogenesis and illustrate that the ERK5 and ERK1/2 kinase cascades play opposing roles regulating MPC cartilage formation. (c) 2010 Wiley-Liss, Inc.

  15. Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression

    Science.gov (United States)

    Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

    2015-01-01

    Aims Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Methods and results Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1–CXCR2 and CX3CL1–CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. Conclusion CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. PMID:25765938

  16. Effects of radiations on bone marrow

    International Nuclear Information System (INIS)

    Tubiana, M.; Frindel, E.; Croizat, H.; Parmentier, C.

    1979-01-01

    After total body irradiation for kidney transplant, the initial decrease of circulating blood cells is more rapid, the nadir is reached sooner and the regeneration occurs earlier when the doses are higher than a few hundred rads. The LD 50 in man seems to be higher than 450 rads. The in vivo and in vitro assays of hemopoietic stem cells have greatly increasedd the understanding of acute and late effects. Multipotential stem cells are very radiosensitive, furthermore the differentiation of the surviving stem cells is accelerated after irradiation. This results in a severe depletion of the stem cell compartment. When this stem cell number falls below a critical value, the stem cell no longer differentiates till the completion of the regeneration of the stem cell compartment. Stem cell proliferation is regulated by inhibitors and stimulators. Release of stimulators by irradiated bone marrow has been demonstrated. Severe sequellae are observed after irradiation of animal and human bone marrow. They seem to be due either to the damage of the stromal cell or to the stem cell population. In patients, four compensating mechanisms are observed after a regional bone marrow irradiation: stimulation of non irradiated bone marrow, extension of hemopoietic areas, regeneration of irradiated bone marrow when the irradiated volume is large and increase in the amplification factor resulting in an increase in the output of mature cells for one stem cell input. Assay of progenitor cells provides useful information and a reduction in their number is still observed many years after a large regional irradiation

  17. Blood and Bone Marrow Donation

    Science.gov (United States)

    ... for a stem cell transplant. Risks Bone marrow donation The most serious risk associated with donating bone ... you feel fully recovered. Peripheral blood stem cell donation The risks of this type of stem cell ...

  18. Bone marrow edema syndrome

    International Nuclear Information System (INIS)

    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E.; Karantanas, Apostolos H.

    2009-01-01

    Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged males. Many hypotheses have been proposed to explain the pathogenesis of the disease. Unfortunately, the etiology of BMES remains obscure. The hallmark that separates BMES from other conditions presented with BME pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Histological examination of the lesion is unnecessary. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is mainly used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are spontaneously resolving, and surgical treatment is not needed. On the other hand, early differential diagnosis and surgical treatment in case of osteonecrosis is of crucial importance. (orig.)

  19. Bone marrow cells other than stem cells seed the bone marrow after rescue transfusion of fatally irradiated mice

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Inoue, T.; Bullis, J.E.

    1987-01-01

    In a previous publication, iodinated deoxyuridine ( 125 IUdR) incorporation data were interpreted as indicating that spleen colony-forming units (CFU-S) in DNA synthesis preferentially seeded bone marrow. In the present studies, the CFU-S content of marrow from irradiated, bone-marrow transfused mice was directly determined. Pretreatment of the transfused cells with cytocidal tritiated thymidine resulted in an insignificant diminution in CFU-S content when compared with nontritiated thymidine pretreatment, implying that there is no preferential seeding. The 125 IUdR incorporation data have been reinterpreted as being a result of the proliferation of other progenitor cells present that have seeded the bone marrow

  20. Comparative studies on the proliferation and differentiation of granulocytic progenitor cells CFU-C from the blood and bone marrow of dogs under normal conditions and after 80 R whole-body irradiation

    International Nuclear Information System (INIS)

    Faul, H.

    1984-01-01

    The study on hand was performed on dogs of both sexes and dealt with two complex issues: 1) the identity of the granulocytic progenitor cell CFU-C in the blood and bone marrow, and 2) possible verification of damage to stem cell store using the granulocytic progenitor cell CFU-C as an indicator for damage caused, in this case, by 80 rd whole body irradiation of dogs. A special culture technique was developed to study these issues, and was tested for its functionability. Examinations of the dogs with whole-body irradiation revealed the following results: a) Radiation damage to the stem cell store could be verified by the study object of CFU-C granulocytic progenitor cell of the bone marrow. A reduction of proliferative capacity linked with a change in the differentiation profiles for the different cell types in the suspension cultures was clearly verified. b) The suspension culture technique allows to verify damage by ionizing radiation both in the acute phase, i.c. two hours after irradiation, and in the late recovery phase. (orig./MG) [de

  1. MRI in bone marrow lesions

    International Nuclear Information System (INIS)

    Linden, A.; Theissen, P.; Schauerte, G.; Schicha, H.; Diehl, V.

    1989-01-01

    MRI has the potential to demonstrate bone marrow pathology due to its good soft tissue contrast. Inflammation and necrosis can be detected very early before there is evidence of radiological changes. In bone tumors intramedullary infiltration can be visualized in addition to soft tissue changes. Metastases of bone and bone marrow, especially in spinal and pelvic regions, are well depicted, often before bone scintigraphy yields pathological findings. In haematological disorders MRI permits follow-up studies due to its good reproducibility. Infiltration by malignant lymphoma and multiple myeloma and its extension in bone marrow can be visualized by MRI, too. However, the most common pathological MRI findings in bone marrow are not very specific, and final diagnosis requires further clinical or histological information. (orig.) [de

  2. Bone marrow contribution to eosinophilic inflammation

    Directory of Open Access Journals (Sweden)

    Denburg Judah A

    1997-01-01

    Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

  3. Peripheral blood progenitor cell transplantation mobilised by r-metHuG-CSF (filgrastim); a less costly alternative to autologous bone marrow transplantation

    NARCIS (Netherlands)

    C.A. Uyl-de Groot (Carin); D.J. Richel (Dirk); F.F.H. Rutten (Frans)

    1994-01-01

    textabstractIn a retrospective study, we calculated the treatment costs of 63 patients who received either autologous bone marrow transplantation (ABMT) with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) (filgrastim) (n=13) or without r-metHuG-CSF (n=22) or altenatively,

  4. Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

    Directory of Open Access Journals (Sweden)

    Rie Kawabe-Yako

    Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

  5. HLA in bone marrow transplantation

    International Nuclear Information System (INIS)

    Tsuji, Kimiyoshi

    1989-01-01

    It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

  6. THE PATHOLOGY OF BONE MARROW FAILURE

    OpenAIRE

    Leguit , Roos; Van Den Tweel , Jan G

    2010-01-01

    Abstract An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerable between childhood and adulthood. In the paediatric age group, inherited bone marrow failure syndromes are important causes of bone marrow failure but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children a...

  7. Bone Marrow Adipocyte Developmental Origin and Biology.

    Science.gov (United States)

    Bukowska, Joanna; Frazier, Trivia; Smith, Stanley; Brown, Theodore; Bender, Robert; McCarthy, Michelle; Wu, Xiying; Bunnell, Bruce A; Gimble, Jeffrey M

    2018-06-01

    This review explores how the relationships between bone marrow adipose tissue (BMAT) adipogenesis with advancing age, obesity, and/or bone diseases (osteopenia or osteoporosis) contribute to mechanisms underlying musculoskeletal pathophysiology. Recent studies have re-defined adipose tissue as a dynamic, vital organ with functions extending beyond its historic identity restricted solely to that of an energy reservoir or sink. "State of the art" methodologies provide novel insights into the developmental origin, physiology, and function of different adipose tissue depots. These include genetic tracking of adipose progenitors, viral vectors application, and sophisticated non-invasive imaging modalities. While constricted within the rigid bone cavity, BMAT vigorously contributes to local and systemic metabolic processes including hematopoiesis, osteogenesis, and energy metabolism and undergoes dynamic changes as a function of age, diet, bone topography, or sex. These insights will impact future research and therapies relating to osteoporosis.

  8. Granulocyte-mobilized bone marrow.

    Science.gov (United States)

    Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

    2012-11-01

    In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

  9. Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors

    Science.gov (United States)

    Avanzini, Maria Antonietta; Bernardo, Maria Ester; Cometa, Angela Maria; Perotti, Cesare; Zaffaroni, Nadia; Novara, Francesca; Visai, Livia; Moretta, Antonia; Del Fante, Claudia; Villa, Raffaella; Ball, Lynne M.; Fibbe, Willem E.; Maccario, Rita; Locatelli, Franco

    2009-01-01

    Background Mesenchymal stromal cells are employed in various different clinical settings in order to modulate immune response. However, relatively little is known about the mechanisms responsible for their immunomodulatory effects, which could be influenced by both the cell source and culture conditions. Design and Methods We tested the ability of a 5% platelet lysate-supplemented medium to support isolation and ex vivo expansion of mesenchymal stromal cells from full-term umbilical-cord blood. We also investigated the biological/functional properties of umbilical cord blood mesenchymal stromal cells, in comparison with platelet lysate-expanded bone marrow mesenchymal stromal cells. Results The success rate of isolation of mesenchymal stromal cells from umbilical cord blood was in the order of 20%. These cells exhibited typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, umbilical cord blood mesenchymal stromal cells may possess high proliferative potential. The genetic stability of these cells from umbilical cord blood was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, do express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune responses, umbilical cord blood mesenchymal stromal cells were able to: (i) suppress T- and NK-lymphocyte proliferation, (ii) decrease cytotoxic activity and (iii) only slightly increase interleukin-10, while decreasing interferon-γ secretion, in mixed lymphocyte culture supernatants. While an indoleamine 2,3-dioxygenase-specific inhibitor did not reverse mesenchymal stromal cell-induced suppressive effects, a prostaglandin E2-specific inhibitor hampered the suppressive effect of both umbilical cord blood- and bone marrow-mesenchymal stromal cells on alloantigen-induced cytotoxic activity. Mesenchymal stromal cells from both sources expressed HLA

  10. Post-irradiation thymocyte regeneration after bone marrow transplantation

    International Nuclear Information System (INIS)

    Boersma, W.; Betel, I.; Daculsi, R.; Westen, G. van der

    1981-01-01

    Growth kinetics of the donor-type thymus cell population after transplantation of bone marrow into irradiated syngeneic recipient mice is biphasic. During the first rapid phase of regeneration, lasting until day 19 after transplantation, the rate of development of the donor cells is independent of the number of bone marrow cells inoculated. The second slow phase is observed only when low numbers of bone marrow cells (2.5 x 10 4 ) are transplanted. The decrease in the rate of development is attributed to an efflux of donor cells from the thymus because, at the same time, the first immunologically competent cells are found in spleen. After bone marrow transplantation the regeneration of thymocyte progenitor cells in the marrow is delayed when compared to regeneration of CFUs. Therefore, regenerating marrow has a greatly reduced capacity to restore the thymus cell population. One week after transplantation of 3 x 10 6 cells, 1% of normal capacity of bone marrow is found. It is concluded that the regenerating thymus cells population after bone marrow transplantation is composed of the direct progeny of precursor cells in the inoculum. (author)

  11. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  12. Bone marrow edema of the knee joint

    International Nuclear Information System (INIS)

    Breitenseher, M.J.; Mayerhoefer, M.E.; Hofmann, S.

    2006-01-01

    Bone marrow edema of the knee joint is a frequent clinical picture in MR diagnostics. It can be accompanied by symptoms and pain in the joint. Diseases that are associated with bone marrow edema can be classified into different groups. Group 1 includes vascular ischemic bone marrow edema with osteonecrosis (synonyms: SONK or Ahlbaeck's disease), osteochondrosis dissecans, and bone marrow edema syndrome. Group 2 comprises traumatic or mechanical bone marrow edema. Group 3 encompasses reactive bone marrow edemas such as those occurring in gonarthrosis, postoperative bone marrow edemas, and reactive edemas in tumors or tumorlike diseases. Evidence for bone marrow edema is effectively provided by MRI, but purely morphological MR information is often unspecific so that anamnestic and clinical details are necessary in most cases for definitive disease classification. (orig.) [de

  13. Bone-marrow transplant - series (image)

    Science.gov (United States)

    Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

  14. Bone and marrow dose modeling

    International Nuclear Information System (INIS)

    Stabin, Michael G.

    2004-01-01

    Nuclear medicine therapy is being used increasingly in the treatment of cancer (thyroid, leukemia/lymphoma with RIT, primary and secondary bone malignancies, and neuroblastomas). In all cases it is marrow toxicity that limits the amount of treatment that can be administered safely. Marrow dose calculations are more difficult than for many major organs because of the intricate association of bone and soft tissue elements. In RIT, there appears to be no consensus on how to calculate that dose accurately, or of individual patients ability to tolerate planned therapy. Available dose models are designed after an idealized average, healthy individual. Patient-specific methods are applied in evaluation of biokinetic data, and need to be developed for treatment of the physical data (dose conversion factors) as well: age, prior patient therapy, disease status. Contributors to marrow dose: electrons and photons

  15. CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter

    2015-01-01

    Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and pro...

  16. Autologous bone marrow purging with LAK cells.

    Science.gov (United States)

    Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

    1993-12-01

    In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

  17. Bone Marrow Matters

    Science.gov (United States)

    Dunne, Mark; Maklad, Rania; Heaney, Emma

    2014-01-01

    As a final-year student teacher specialising in primary science, Emma Heaney faced the challenge of having to plan, organise, and conduct a small-scale, classroom-based research project. She had to teach about bones in the final block practice session and thought it would be a good idea to bring in some biological specimens obtained from the local…

  18. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

    Science.gov (United States)

    Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

    2017-03-07

    Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Gillick, bone marrow and teenagers.

    Science.gov (United States)

    Cherkassky, Lisa

    2015-09-01

    The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.1 of the Children Act 1989? There are no legal authorities on child bone marrow harvests in the United Kingdom. This article considers the best interests of the older saviour sibling and questions whether, for the purposes of welfare, the speculative benefits could outweigh the physical burdens. © The Author(s) 2015.

  20. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

    Science.gov (United States)

    Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

    2009-01-01

    Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

  1. Bone marrow edema in sports: General concepts

    International Nuclear Information System (INIS)

    Vanhoenacker, F.M.; Snoeckx, A.

    2007-01-01

    This paper will discuss the value of medical imaging in the detection and follow-up of bone marrow edema (BME), resulting from acute and chronic trauma in sports. MR imaging is the only imaging technique that allows direct evaluation of bone marrow edema in sports medicine. The use of fat suppressed T2-weighted or STIR images is particularly appropriate to detect bone marrow edema. The extent of bone marrow edema reflects the biomechanics of trauma. Compressive forces between two bony structures will result in extensive areas of bone marrow edema, whereas distraction forces provoke more subtle areas of bone marrow edema at the insertion of supporting structures of joints. In most clinical situations, a combination of compression and distraction forces is present, causing a complex pattern of bone marrow edema. A meticulous pattern approach of the distribution of these bone marrow changes around a joint can reveal in most instances the underlying mechanism of trauma. This may be helpful to analyze which joint supporting structures may be at risk. In the acute setting, plain radiography and CT scan may have an additional role in the detection of small avulsion fractures occurring at the site of minor areas of bone marrow edema. The clinical significance and natural history of bone marrow edema is still a matter of debate

  2. MR imaging of normal bone marrow

    International Nuclear Information System (INIS)

    Stajgis, M.; Paprzycki, W.

    1994-01-01

    Principles of MR bone marrow imaging on the basis of retrospective analysis of MR examinations of bone marrow in different anatomic sites in 200 patients have been discussed. Significance of different physiologic factors and processes such as age, steatosis, osteoporosis, conversion and reconversion, which influence on MR bone marrow images, have been emphasized. T1-weighted images obtained with spin-echo sequences give the most of information about bone marrow structure in MR. Thorough knowledge of bone marrow physiology and clinical status of the patient is indispensable in correct interpretation of hypointensive lesions on T1-weighted images. When presence of disseminated bone marrow disease is suspected, authors propose routine imaging of lumbar vertebral column, pelvis and proximal parts of femoral bones. (author)

  3. Patterns of bone-marrow scintigraphy

    International Nuclear Information System (INIS)

    Touya, J.J.; Lee, G.S.; Narvaez, M.; Marciano, D.

    1977-01-01

    111 In-transferrin, radiocolloid and bone scans were performed within one week on 105 from more than 250 scanned patients with different haematological disorders. All patients had complete haematological workups and confirmed final diagnoses. From the comparison of the 111 In-transferrin marrow scan with the radiocolloid marrow scan and bone scan, eight basic patterns of localized or generalized disorders in the bone marrow cell production were delineated. The first pattern was called a cold area and two sub-patterns were distinguished in it. A cold area in the erythropoietic and reticuloendothelial scans associated with cold or normal areas in the bone scan corresponded to radiation damage of the marrow or multiple myeloma; a cold area in both marrow scans with a hot area in the bone scan to tumour, infarct and bone trauma. The second pattern was called a hot area. A hot area in the two marrow scans with a normal bone scan was observed in islands of active bone-marrow. Hot areas in both 111 In-transferrin and bone scan associated with a cold area in the radiocolloid scan were observed in tumours growing in bones with or without little active bone marrow. Hot areas on the three scans were observed in osteomyelitis of bones of the extremities. The third pattern was bone-marrow expansion, which was observed in hereditary haemolytic anaemias, in myeloproliferative disorders and in patients with bone-marrow damage following irradiation. The fourth pattern was saturation of the serum iron-binding capacity and it was manifested by increased activity in the kidneys in the 111 In-transferrin scan. The fifth pattern was bone-marrow failure which consists of decreased accumulation in the marrow and increased accumulation in the liver of marrow-seeking agents associated with normal bone scan. The sixth pattern, pure red cell aplasia, was characterized by less accumulation of 111 In-transferrin than radiocolloid in the bone marrow. The seventh pattern, bone-marrow siderosis

  4. Bone marrow ablation with Ho-166 pharmaceuticals as preparation for bone marrow transplants

    International Nuclear Information System (INIS)

    Parks, N.J.; Kawakami, T.; Avila, M.; White, R.; Cain, G.; Moore, P.F.

    1991-01-01

    Bone marrow ablation is required preparation for leukemia patients where bone marrow transplantation is to be the therapeutic modality. Presently, the total body irradiation that is used produces appreciable morbidity in terms of radiation sickness, but an evenly distributed dose to marrow. The authors have shown in Beagles that bone-seeking radiolanthanide (Ho-166, t 1/2 = 25 h, 1.8 MeB beta, carrier added) phosphonic acid chelates can be used to completely ablate bone marrow with little morbidity. The research plan, incorporating bone marrow ablation with bone-seeking radionuclides and in vitro purging of aspirated leukemic marrow for use in autologous marrow transplants, is presented. Phosphonic acid complexes of Sm-153 also localize in the skeleton and have found use in the palliation of bone pain. However, the dose distribution is uneven because these radiopharmaceuticals distribute according to available surface; 2-4 times the skeletal average in trabecular vs cortical bone. Thus, the marrow dose can vary. The authors' research group and the Radiation Interactions Division of NIST have announced the discovery that beta radiation-induced excited electrons are trapped in the hydroxyapatite mineral of bone and provide a potential direct dosimetric method for marrow dose when combined with routine bone marrow (and included bone) biopsies. The overall research plan sets the hypothesis that reduced morbidity marrow ablation can be successfully followed by bone marrow transplantation (BMT) with autologous marrow purged in vitro by antibody-targeted alpha emitters

  5. Persistent injury-associated anemia: the role of the bone marrow microenvironment.

    Science.gov (United States)

    Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

    2017-06-15

    The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. MR appearances of bone marrow in children following bone marrow transplantation

    International Nuclear Information System (INIS)

    Boothroyd, A.E.; Sebag, G.; Brunelle, F.

    1991-01-01

    Two cases are presented of children who demonstrated complete absence of bone marrow signal on MR imaging of the spine following bone marrow transplantation. The possible causes for these appearances are discussed. (orig.)

  7. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  8. Starvation marrow – gelatinous transformation of bone marrow

    Directory of Open Access Journals (Sweden)

    Eric Osgood

    2014-09-01

    Full Text Available Gelatinous bone marrow transformation (GMT, also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management.

  9. Magnetic resonance imaging of the bone marrow

    International Nuclear Information System (INIS)

    Baur-Melnyk, Andrea

    2013-01-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  10. Magnetic resonance imaging of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2013-08-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  11. The Bone Marrow-Derived Stromal Cells

    DEFF Research Database (Denmark)

    Tencerova, Michaela; Kassem, Moustapha

    2016-01-01

    Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone...... diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage...

  12. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Science.gov (United States)

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  13. How to exhaust your bone marrow

    DEFF Research Database (Denmark)

    Salomo, Louise; Salomo, Morten; Andersen, Steven A W

    2013-01-01

    at work and in his spare time, and kept a very thorough training and weight diary. Owing to a high intake of energy and protein drinks he tried to optimise his physical performance and kept a normal body mass index  at 23.7. A bone marrow biopsy showed gelatinous bone marrow transformation, normally seen...

  14. Functional bone marrow scintigraphy in psoriatics

    International Nuclear Information System (INIS)

    Munz, D.; Altmeyer, P.; Chilf, G.; Schlesinger, G.; Holzmann, H.; Hoer, G.

    1982-01-01

    24 psoriatics as well as 24 normal healthy adults were studied by functional bone marrow scintigraphy using Tc-99m-labeled human serum albumin millimicrospheres (Tc-99m-HSA-MM). Functional bone marrow scintigraphy is an in vivo test system for the assessment of various functional properties of fixed macrophages. 58% of psoriatics who had no systemic drug treatment demonstrated peripheral extension of the bone marrow space indicating hyperplasia of bone marrow macrophages. This phenomenon could be observed only in one normal subject who was a high-performance sportsman. 83% (n=6) of psoriatics with cirrhosis of liver demonstrated bone marrow extension. The 'capacity' of bone marrow macrophages to engulf Tc-99m-HSA-MM ('uptake ratio') was diminished in 42% of non-treated as well as 66% of psoriatics treated with aromatic retinoid. The phagocytic and proteolytic turnover of Tc-99m-HSA-MM in bone marrow, spleen, and liver was found to be accelerated in 66% of non-treated psoriatics, normal, accelerated or delayed in psoriatics treated with aromatic retinoid as well as considerably delayed in all of the psoriatics with cirrhosis of liver. Functional bone marrow scintigraphy proved to be an appropriate in vivo test system to reveal abnormalities of fixed macrophages in psoriatics. Furthermore, theratpeutic effects as well as influences of pre-existing disorders on different macrophage populations can be assessed. (Author)

  15. Clinical aspects of bone marrow transplantation

    International Nuclear Information System (INIS)

    Shmitts, N.; Gassmann, V.; Leffler, G.

    1986-01-01

    Experience of bone marrow transplantation into patients with myeloproliferative syndromes, myelodysplasias and highly malignant lymphomas is presented. Side early and late effects of transplantation are described. The frequency and severity of complications of bone marrow transplantation depend sufficiently on the disease as well as on patient's age and general condition

  16. [Endogenous pyrogen formation by bone marrow cells].

    Science.gov (United States)

    Efremov, O M; Sorokin, A V; El'kina, O A

    1978-01-01

    The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

  17. Bone-Marrow Storage and Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Costachel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N. [Oncological Institute, Bucharest (Romania)

    1969-07-15

    The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: Bullet Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. Bullet While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. Bullet No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4 Degree-Sign C. Bullet DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. Bullet In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: Bullet The best time to administer bone marrow is between 24 and 48 h after irradiation. Bullet No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. Bullet Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. Bullet In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of

  18. Bone-Marrow Storage and Transplantation

    International Nuclear Information System (INIS)

    Costăchel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N.

    1969-01-01

    The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: • Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. • While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. • No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4°C. • DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. • In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: • The best time to administer bone marrow is between 24 and 48 h after irradiation. • No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. • Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. • In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of certain typical signs of secondary syndrome

  19. MR imaging of bone marrow disorders

    International Nuclear Information System (INIS)

    Yoshida, H.; Mano, I.; Yashiro, N.; Asai, S.; Lio, M.

    1986-01-01

    The author performed MR imaging in 89 patients with bone marrow disorders (29 with aplastic anemia, 20 with leukemia, 9 with postirradiation changes, 8 with hemosiderosis, 6 with primary bone tumors and metastases, and 17 with bone marrow disorders of other etiologies). They selected the thoracic and lumbar vertebral marrow as a target and used both T1-weighted spin-echo images and calculated T1 images. T1 was prolonged in bone marrow hyperplasia but shortened in hypoplasia. Bone marrow T1 values proved to depend on the number of fat cells (pathologic correlation). In aplastic anemia scattered islands of low signal intensity were seen within a background of high signal intensity in some typical cases. MR imaging patterns were used for staging aplastic anemia. T1 was prolonged in leukemia cells

  20. Irradiation of the red bone marrow and the health implications ...

    African Journals Online (AJOL)

    The physiology and function of the bone is looked at as to the role in housing bone marrow. The bone marrow and particularly the red bone marrow is discussed. Sources of radiation are discussed and the health implications highlighted for caution and for study or evaluation. Key Words: Bone marrow, Irradiation, Radiation, ...

  1. Bone marrow transplantation after irradiation

    International Nuclear Information System (INIS)

    Koch, M.; Blaha, M.; Merka, V.

    1990-01-01

    Bone marrow transplantation after irradiation is successful in only a part of the affected patients. The Chernobyl accident added to our knowledge: BMT can save life after whole-body irradiation with a dose exceeding 7-8 Gy. A timely decision on transplantation after a nuclear accident is difficult to make (rapid determination of homogeneity and type of radiation and the total dose. HL-A typing in lymphopenia, precise identification of radiation damage to other target organs, etc.). Further attention is to be paid to the treatment. Transplantations in case of malignities (especially hematologic ones) and other diseases will add to our knowledge and will lead to more simple procedures. (author). 3 figs., 1 tab., 12 refs

  2. Bone marrow oedema associated with benign and malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

    2008-07-15

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

  3. Relative 238Pu content of bone and bone marrow

    International Nuclear Information System (INIS)

    McClanahan, B.J.

    1979-01-01

    Selected bones from a dog that inhaled 238 PuO 2 were subjected to ultrasonic cell disruption to separate the marrow elements from bone, in order to determine the plutonium content of the two components of the skeleton

  4. Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0234 TITLE: Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion PRINCIPAL...14/2017 4. TITLE AND SUBTITLE Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion 5a. CONTRACT NUMBER 5b. GRANT...tolerance induction of all types of allografts. In this study, we investigate whether co-infusion of amnion- derived multipotent progenitor (AMP) cells

  5. Can bone marrow differentiate into renal cells?

    Science.gov (United States)

    Imai, Enyu; Ito, Takahito

    2002-10-01

    A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

  6. Bone Marrow Transplantation: MedlinePlus Health Topic

    Science.gov (United States)

    ... marrow transplant - discharge (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Bone Marrow Transplantation ... transplant - slideshow Graft-versus-host disease Related Health Topics Bone Marrow Diseases Stem Cells National Institutes of ...

  7. Bone- and bone marrow scintigraphy in Gaucher disease type 1

    International Nuclear Information System (INIS)

    Mikosch, P.; Zitter, F.; Gallowitsch, H.J.; Lind, P.; Wuertz, F.; Mehta, A.B.; Hughes, D.A.

    2008-01-01

    Scintigraphy is a method for imaging metabolism and should be viewed as complimentary to morphological imaging. Bone and bone marrow scintigraphy can particularly contribute to the detection of focal disease in Gaucher disease. In bone crises it can discriminate within three days after pain onset between local infection and aseptic necrosis. A further advantage of bone- and bone marrow scintigraphy is the visualization of the whole skeleton within one setting. Whole body imaging for focal lesions might thus be an objective in GD, in particular in patients complaining of several painful sites. Direct imaging of bone marrow deposits in GD by MIBI scintigraphy might be of special interest in children in whom bone marrow undergoes a developmental conversion from red to yellow marrow in the ap-pendicular skeleton. MRI interpretation in young GD patients is thus difficult in order to estimate the exact amount and extent of bone marrow infiltration by Gaucher cells. 99mTc-MIBI scintigraphy with its direct visualization of lipid storage could thus add interesting additional information not shown with other methods including MRI. Although MRI is the most accepted imaging modality in assessing the skeletal status in GD, a selective use of scintigraphy for imaging bone and bone marrow may add information in the evaluation of patients with Gaucher disease

  8. Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

    Science.gov (United States)

    Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

    2015-11-01

    During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

  9. Bone marrow lesions: A systematic diagnostic approach

    International Nuclear Information System (INIS)

    Grande, Filippo Del; Farahani, Sahar J; Carrino, John A; Chhabra, Avneesh

    2014-01-01

    Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted

  10. Thalassemia paravertebral tumors and bone marrow scan

    International Nuclear Information System (INIS)

    Huglo, D.; Rose, C.; Deveaux, M.; Bauters, F.; Marchandise, X.

    1995-01-01

    Two first cousins with thalassemia and with a paravertebral mass had had an indium 111 chloride bone marrow scan. Result of scan influenced therapy: medical treatment in one case where an extramedullary erythropoiesis was confirmed, surgical treatment in the other case. The use of dual-isotope SPECT (indium 111 chloride, HDP -99 Tc) constitutes a contribution to the establishment of diagnosis of extramedullary erythropoiesis, giving to bone marrow scintigraphy a merited importance, avoiding the biopsy. (authors). 15 refs., 5 figs

  11. Bone marrow lesions: A systematic diagnostic approach

    Directory of Open Access Journals (Sweden)

    Filippo Del Grande

    2014-01-01

    Full Text Available Bone marrow lesions on magnetic resonance (MR imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI, to achieve accurate final diagnosis has been highlighted.

  12. BONE MARROW ABONRMALITIES IN HIV INFECTION

    OpenAIRE

    Sharad Antiram Dhurve

    2013-01-01

    Introduction Hematological abnormalities are a common complication of HIV infection. Bone marrow abnormalities occur in all stages of HIV infection. Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS. Methods 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4 counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AID...

  13. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2. The bone marrow distribution in leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

    1976-04-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia.

  14. Reintegration after bone marrow transplantation.

    Science.gov (United States)

    Baker, F; Zabora, J; Polland, A; Wingard, J

    1999-01-01

    This study examines the problems of bone marrow transplantation (BMT) survivors in returning to "normal" life in the community after BMT. Before being released from The Johns Hopkins Oncology Center, 84 recipients of BMT were interviewed regarding their quality of life and psychosocial adaptation. Survivors were reinterviewed at 6 months, and at 1 year post-BMT, producing considerable qualitative data regarding their problems in living. Eighty-four patients who had received BMT completed qualitative interviews and standardized measures before treatment, before the return home, and at 6 and 12 months post-BMT. The interviews were subjected to a content analysis methodology to establish units and categories to examine the body of material. Content analysis of these interviews from the first year after BMT identified three areas of psychosocial morbidity; 1) physical problems, which included fatigue, appearance, troubles in eating, and physical restrictions; 2) psychological problems, which included fears about the future, sense of loss of control, anxiety, and depression; and 3) community reintegration problems, which included difficulty in returning to former social roles, separation from home, family, and friends, difficulty in resuming social relations, dealing with stigmatization, problems with family and children, and financial and employment difficulties. Identification of these problems for BMT survivors can be used to guide the development of specific materials and services to prepare recipients of BMTs and their families for life after the transplant. These qualitative results can also be used to direct the development of assessment tools to identify potential patient and family problems.

  15. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  16. Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

    International Nuclear Information System (INIS)

    Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

    1982-01-01

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

  17. SERPINB2 is a novel TGFβ-responsive lineage fate determinant of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad

    2017-01-01

    TGF-β1, a multifunctional regulator of cell growth and differentiation, is the most abundant bone matrix growth factor. During differentiation of human bone stromal cells (hBMSCs), which constitute bone marrow osteoblast (OS) and adipocyte (AD) progenitor cells, continuous TGF-β1 (10 ng/ml) treat...

  18. Paracrine effects and heterogeneity of marrow-derived stem/progenitor cells: relevance for the treatment of respiratory diseases.

    Science.gov (United States)

    Conese, Massimo; Carbone, Annalucia; Castellani, Stefano; Di Gioia, Sante

    2013-01-01

    Stem cell-based treatment may represent a hope for the treatment of acute lung injury and pulmonary fibrosis, and other chronic lung diseases, such as cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). It is well established in preclinical models that bone marrow-derived stem and progenitor cells exert beneficial effects on inflammation, immune responses and repairing of damage in virtually all lung-borne diseases. While it was initially thought that the positive outcome was due to a direct engraftment of these cells into the lung as endothelial and epithelial cells, paracrine factors are now considered the main mechanism through which stem and progenitor cells exert their therapeutic effect. This knowledge has led to the clinical use of marrow cells in pulmonary hypertension with endothelial progenitor cells (EPCs) and in COPD with mesenchymal stromal (stem) cells (MSCs). Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells, MSCs, EPCs and fibrocytes, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine and applied to lung disorders. Copyright © 2013 S. Karger AG, Basel.

  19. An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

    Science.gov (United States)

    Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

    2017-06-01

    Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

  20. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  1. Bone marrow fibrosis – the basis of mielofibrosis: pathogenesis, prognostication and antifibrogenic targeted strategies

    Directory of Open Access Journals (Sweden)

    Timchenko A.S.

    2018-03-01

    Full Text Available Bone marrow fibrosis is a key patological feature and major diagnostic criterion of mielofibrosis. Although bone marrow fibrosis is manifested in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the mielofibrosis of hematopoietic stem/progenitor cells, contributing to an impaired microenvironment toward malignant over normal hematopoiesis. The increased expression of pro­inflammatory cytokines, transforming growth factor-β, impaired megakaryocyte function and aberrant JAK-STAT signaling are the peculiarities of pathogenesis of bone marrow fibrosis. Hematopoietic stem cell transplantation remains the only therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with mielofibrosis. In the work we review the pathogenesis, biological consequences and prognostic results of impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting at clonal hematopoietic stem/progenitor cells, aberrant signaling pathway, fibrogenic cytokines, and tumor microenvironment.

  2. Morphological Manifestations of Parvovirus B19 Infection in the Bone Marrow.

    Science.gov (United States)

    1997-01-09

    Parvovirus B19 (PV B19 ) preferentially infects erythroid progenitor cells in the bone marrow, frequently causing anemia along with transient aplastic...infection. We devised a highly sensitive two-round, nested PCR procedure to detect PV B19 . Eight of 78 clinical specimens from individuals with

  3. Shifting bone marrow edema of the knee

    International Nuclear Information System (INIS)

    Moosikasuwan, Josh B.; Schultz, Elizabeth; Miller, Theodore T.; Math, Kevin

    2004-01-01

    The purpose of our study is to describe shifting bone marrow edema in the knee as the MR imaging feature of intra-articular regional migratory osteoporosis of the knee. Five men, aged 45-73 years, were referred by orthopedic surgeons for MR imaging evaluation of knee pain, which had been present for 2 weeks to 6 months. One patient had a prior history of blunt trauma. None had risk factors for osteonecrosis. Four patients had two MR examinations and the patient with prior blunt trauma had four. Plain radiographs were obtained in all patients. In all cases, a large area of marrow edema initially involved a femoral condyle, with migration of the bone marrow edema to the other femoral condyle, tibia, and/or patella occurring over a 2- to 4-month period. Adjacent soft tissue edema was present in all five patients, while none had a joint effusion. Radiographs of two patients showed generalized osteopenia. In the absence of acute trauma or clinical suspicion of infection, a large area of bone marrow edema without a zone of demarcation may represent intra-articular regional migratory osteoporosis. Demonstration of shifting bone marrow edema on follow-up examinations suggests this diagnosis. (orig.)

  4. BONE MARROW ABONRMALITIES IN HIV INFECTION

    Directory of Open Access Journals (Sweden)

    Sharad Antiram Dhurve

    2013-06-01

    Full Text Available ABSTRACT Introduction; Hematological abnormalities are a common complication of HIV infection.  Bone marrow abnormalities occur in all stages of HIV infection.  Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS.  Methods: 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4   counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AIDS and those without AIDS according to NACO criteria.   Bone marrow examination was performed for indication of anemia, leucopenia, pancytopenia and thrombocytopenia. Results: As per CDC criteria 59.81% patients had AIDS in 107 patients. The most common hematological abnormality was anemia, seen in 93.12% patients.  Bone marrow was normocellular in 79.06% of non-AIDS and 79.68% of AIDS, hypocellular in 13.95%.Thrombocytopenia was seen in 4 cases of ART (4.93% and 3 cases (4.68% of AIDS group. Abnormal cells like plasma cell, histocyte and toxic granule found in bone marrow. Conclusions: Myelodysplasia was more common in AIDS than in non AIDS patients. Granulocytic series is most commonly associated with evidence of dysplasia. Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Thus bone marrow study is imperative to methodically observe and follow clinical and laboratory aberration in such patients in order to improve our diagnostic and therapeutic skills pertinent to HIV/AIDS.

  5. Multifocal bone and bone marrow lesions in children - MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Raissaki, Maria; Demetriou, Stelios; Spanakis, Konstantinos; Skiadas, Christos; Karantanas, Apostolos H. [University of Crete, Faculty of Medicine, Department of Radiology, University Hospital of Heraklion, Heraklion, Crete (Greece); Katzilakis, Nikolaos; Stiakaki, Eftichia [University of Crete, Faculty of Medicine, Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Crete (Greece); Velivassakis, Emmanouil G. [University Hospital of Heraklion, Orthopedic Clinic, Heraklion, Crete (Greece)

    2017-03-15

    Polyostotic bone and bone marrow lesions in children may be due to various disorders. Radiographically, lytic lesions may become apparent after loss of more than 50% of the bone mineral content. Scintigraphy requires osteoblastic activity and is not specific. MRI may significantly contribute to the correct diagnosis and management. Accurate interpretation of MRI examinations requires understanding of the normal conversion pattern of bone marrow in childhood and of the appearances of red marrow rests and hyperplasia. Differential diagnosis is wide: Malignancies include metastases, multifocal primary sarcomas and hematological diseases. Benign entities include benign tumors and tumor-like lesions, histiocytosis, infectious and inflammatory diseases, multiple stress fractures/reactions and bone infarcts/ischemia. (orig.)

  6. Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

    Science.gov (United States)

    Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

    2017-03-01

    Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    Science.gov (United States)

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-07

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

  8. Diffusion and perfusion imaging of bone marrow

    International Nuclear Information System (INIS)

    Biffar, Andreas; Dietrich, Olaf; Sourbron, Steven; Duerr, Hans-Roland; Reiser, Maximilian F.; Baur-Melnyk, Andrea

    2010-01-01

    In diffusion-weighted magnetic resonance imaging (DWI), the observed MRI signal intensity is attenuated by the self-diffusion of water molecules. DWI provides information about the microscopic structure and organization of a biological tissue, since the extent and orientation of molecular motion is influenced by these tissue properties. The most common method to measure perfusion in the body using MRI is T1-weighted dynamic contrast enhancement (DCE-MRI). The analysis of DCE-MRI data allows determining the perfusion and permeability of a biological tissue. DWI as well as DCE-MRI are established techniques in MRI of the brain, while significantly fewer studies have been published in body imaging. In recent years, both techniques have been applied successfully in healthy bone marrow as well as for the characterization of bone marrow alterations or lesions; e.g., DWI has been used in particular for the differentiation of benign and malignant vertebral compression fractures. In this review article, firstly a short introduction to diffusion-weighted and dynamic contrast-enhanced MRI is given. Non-quantitative and quantitative approaches for the analysis of DWI and semiquantitative and quantitative approaches for the analysis of DCE-MRI are introduced. Afterwards a detailed overview of the results of both techniques in healthy bone marrow and their applications for the diagnosis of various bone-marrow pathologies, like osteoporosis, bone tumors, and vertebral compression fractures are described.

  9. Bone--bone marrow interface (endosteum) potential relationship of microenvironments in the regulation of response to internal emitters

    International Nuclear Information System (INIS)

    Wilson, F.D.; Pool, R.R.; Stitzel, K.; Momeni, M.H.

    1976-01-01

    The interface between bone and bone marrow is examined in relation to radiation effects, with attention to new concepts of hematopoiesis. Such concepts propose a functional role of stroma in regulating the commitment of pluripotent stem cells as well as in the production of colony stimulating activity (CSA) including candidate granulopoietin(s). Morphologic examples are included, underlining the concept that stroma (including bone) and hematopoietic elements respond as a functional unit to injury to marrow elements. The methylcellulose bone marrow culture system is reviewed as it may relate to a method for quantitation of hematopoietic colonies (CFU-C), humoral regulators for granulopoiesis (CSA), and potentially as a method of quantitating mesenchymal progenitor populations (PFU-C). Based on these and other observations cited, a model depicting a tentative positioning of cells at risk relative to bone-seeking radionuclides is presented

  10. Normal human bone marrow and its variations in MRI

    International Nuclear Information System (INIS)

    Vahlensieck, M.; Schmidt, H.M.

    2000-01-01

    Physiology and age dependant changes of human bone marrow are described. The resulting normal distribution patterns of active and inactive bone marrow including the various contrasts on different MR-sequences are discussed. (orig.) [de

  11. Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Vannucchi, Alessandro M; Migliaccio, Anna Rita

    2007-01-01

    BACKGROUND AND OBJECTIVES: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from...

  12. Biochemical markers predictive for bone marrow involvement in systemic mastocytosis

    NARCIS (Netherlands)

    Donker, Marjolein L.; van Doormaal, Jasper J.; van Doormaal, Frederiek F.; Kluin, Philip M.; van der Veer, Eveline; de Monchy, Jan G. R.; Kema, Ido P.; Kluin-Nelemans, Hanneke C.

    Systemic mastocytosis is characterized by bone marrow involvement, which requires a bone marrow biopsy for diagnostic work-up. We questioned whether bone marrow involvement could be predicted using biochemical markers. We selected patients with various symptoms suggestive of indolent systemic

  13. The Role od Bone Marrow Aspirate and Trephine Samples in ...

    African Journals Online (AJOL)

    Other disorders diagnosed after bone marrow examination include myelodysplastic syndrome (MDS), aplastic anaemia, megaloblastic anaemia and myelofibrosis. Only 8.75% of these patients had a normal bone marrow. Conclusions: This study has demonstrated the complexity of using bone marrow examination in ...

  14. Intractable Diseases Treated with Intra-Bone Marrow-Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-09-01

    Full Text Available Bone marrow transplantation (BMT is used to treat hematological disorders, autoimmune diseases and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells but also mesenchymal stem cells (MSMCs. MSMCs are multi-potent stem cells that can be isolated from bone marrow, umbilical cord blood, and adipose tissue. MSMCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSMCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of bone marrow-derived- MSMCs, and the treatment of intractable diseases such as rheumatoid arthritis and malignant tumors with IBM-BMT.

  15. PET in Benign Bone Marrow Disorders

    NARCIS (Netherlands)

    van der Bruggen, Wouter; Glaudemans, Andor W. J. M.; Vellenga, Edo; Slart, Riemer H. J. A.

    This review aims to describe the current status of benign bone marrow (BM) imaging using PET. BM imaging is important as the BM is not only involved in poiesis of different vital cell lines and. can be affected by primary BM disorders, but it is also frequently affected by several extramedullary

  16. Diabetes Mellitus Induces Bone Marrow Microangiopathy

    NARCIS (Netherlands)

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P. J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Objective-The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results-We found profound structural alterations in BM from mice with

  17. Allogeneic and Autologous Bone-Marrow Transplantation

    OpenAIRE

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments.

  18. Periapical multilocular osteoporotic bone marrow defect

    International Nuclear Information System (INIS)

    Jung, Yun Hoa; Cho, Bong Hae; Nah, Kyung Soo

    2005-01-01

    A case of osteoporotic bone marrow defect, which appeared as a well-defined multilocular radiolucency overlapping the roots of mandibular right second molar, was reported. On periapical radiograph, a daughter cyst-like radiolucency was seen at the anterior margin of the lesion making it difficult to rule out odontogenic keratocyst.

  19. Periapical multilocular osteoporotic bone marrow defect

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yun Hoa; Cho, Bong Hae; Nah, Kyung Soo [Pusan National University College of Medicine, Busan (Korea, Republic of)

    2005-12-15

    A case of osteoporotic bone marrow defect, which appeared as a well-defined multilocular radiolucency overlapping the roots of mandibular right second molar, was reported. On periapical radiograph, a daughter cyst-like radiolucency was seen at the anterior margin of the lesion making it difficult to rule out odontogenic keratocyst.

  20. Bone marrow examination: Indications and diagnostic value

    International Nuclear Information System (INIS)

    Bashawri, Layla A.

    2002-01-01

    Objective was to identify the main indications for bone marrow examination in a University hospital setup and the most common diagnoses encountered. To also identify the extent of correlation, if any, between the preliminary diagnosis and the result of the final bone marrow diagnosis. The requests and reports of all bone marrow biopsies and aspirations carried out during a 12-year period from January 1988 through to December 1999, in King Fahd Hospital of the University, Al Khobar, Kingdom of Saudi Arabia were retrospectively reviewed. The information extracted included the main indications for performing this procedure, age groups involved, and the most common diagnoses encountered. A specially designed form was used for this purpose and the data was analyzed using the statistical package for social sciences. Randomly selected slides of the most common diagnoses were reviewed to concur with the diagnosis. There was a total of 1813 bone marrow biopsies or aspirations, or both, performed. The main indications for bone marrow examination in a descending order of frequency were the following: The diagnosis and management of acute leukemia 403 (22.2%), staging for lymphoma 276 (15.2%), evaluation of pancytopenia 215 (11.9%), thrombocytopenia 173 (9.5%), investigation of anemia 151 (8.3%), fever (pyrexia of unknown origin) 130 (7.2%), lymphadenopathy 120 (6.6%), and hepatosplenomegaly 80 (4.4%). The most common diagnoses encountered were: acute lymphoblastic leukemia 242 (13.3%), immune thrombocytopenia 123 (6.8%), acute myeloblastic leukemia 80 (4.4%), hypersplenism 79 (4.4%), chronic granulocytic leukemia 73 (4.0%), megaloblastic anemia 66 (3.6%), bone marrow positive for lymphomatous infiltration 63 (3.5%), chronic lymphocytic leukemia 40 (2.2%), and multiple myeloma 32 (1.8%). This study confirms that bone marrow examination is a very important investigation for establishing the diagnosis in many conditions, especially hematological neoplasms. The most common

  1. Bone marrow scintigraphy in hemopoietic depletion states

    International Nuclear Information System (INIS)

    Fortynova, J.; Bakos, K.; Pradacova, J.

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and 111 InCl 3 ;some patients were examined using both indicators. 111 InCl 3 is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or 111 InCl 3 is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia. (author)

  2. Bone marrow scintigraphy in hemopoietic depletion states

    Energy Technology Data Exchange (ETDEWEB)

    Fortynova, J. (Ustav Hematologie a Krevni Transfuze, Prague (Czechoslovakia)); Bakos, K.; Pradacova, J. (Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav)

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and /sup 111/InCl/sub 3/; some patients were examined using both indicators. /sup 111/InCl/sub 3/ is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or /sup 111/InCl/sub 3/ is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia.

  3. Abscopal suppression of bone marrow erythropoiesis

    International Nuclear Information System (INIS)

    Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

    1978-01-01

    Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

  4. Magnetic resonance imaging of the bone marrow in hematological malignancies

    International Nuclear Information System (INIS)

    Berg, B.C. vande; Lecouvet, F.E.; Maldague, B.; Malghem, J.; Michaux, L.; Ferrant, A.

    1998-01-01

    Despite its lack of specificity, magnetic resonance imaging (MRI) of the bone marrow has the potential to play a role in the management of patients with primary neoplastic disorders of the hematopoietic system, including lymphomas, leukemias and multiple myeloma. In addition to its use in the assessment of suspected spinal cord compression, bone marrow MRI could be used as a prognostic method or as a technique to assess the response to treatment. The current review addresses the common patterns of bone marrow involvement observed in primary neoplasms of the bone marrow, basic technical principles of bone marrow MRI, and several applications of MRI in selected clinical situations. (orig.) (orig.)

  5. Marrow uptake index (MUI): A quantitative scintigraphic study of bone marrow in aplastic anaemia

    International Nuclear Information System (INIS)

    Padhy, A.K.; Garg, A.; Kochupillai, V.; Gopinath, P.G.; Basu, A.K.

    1987-01-01

    Aplastic anaemia affects the entire bone marrow. This prospective study was undertaken to develop and standardise a new nuclear medicine technique called 'dynamic bone marrow imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99m Tc S. Colloid, and an index, called the bone marrow uptake index was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. 20 refs.; 4 figs.; 5 tabs

  6. Karyotype of cryopreserved bone marrow cells

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    M.L.L.F. Chauffaille

    2003-07-01

    Full Text Available The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis. Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05. Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05. GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

  7. Karyotype of cryopreserved bone marrow cells.

    Science.gov (United States)

    Chauffaille, M L L F; Pinheiro, R F; Stefano, J T; Kerbauy, J

    2003-07-01

    The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases) to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis). Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively) were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05). Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05). GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

  8. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2

    International Nuclear Information System (INIS)

    Fujimori, Katsuhiko

    1976-01-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia. (J.P.N.)

  9. Molecular Mechanisms That Contribute to Bone Marrow Pain

    Directory of Open Access Journals (Sweden)

    Jason J. Ivanusic

    2017-09-01

    Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

  10. Postirradiation bone marrow damage in chickens

    International Nuclear Information System (INIS)

    Skardova, I.; Ojeda, F.

    1994-01-01

    The frequency of bone marrow damage induced by the continuous gamma irradiation was studied. Effect of dose rate and level of cumulated doses of radiation was evaluated in clinical and hematological examinations and bone marrow damage was determined by chromosome aberrations in anaphase. The regulative ability of hematopoiesis of many cytokines are discussed. Positive regulators are inducers of cell proliferation, and negative regulators are inducers of apoptosis /programmed cell death/. Birds corresponding with similarities in thymus-T and bursal-B cells appear to be an interesting model for studying the possible participation of apoptosis in radiation disease. Our recent experimental studies continue to progress in this direction. (author) 17 refs.; 3 figs.; 2 tabs

  11. Bone marrow transplantation for childhood malignancies

    International Nuclear Information System (INIS)

    Toyoda, Yasunori

    1992-01-01

    As of June 30, 1991, 1013 pediatric patients had registrated to The Bone Marrow Transplantation Committee of the Japanese Society of Pediatric Hematology. Bone marrow transplantation (BMT) from HLA-matched siblings is now reasonably safe and an established method of treatment in acute leukemia. Total body irradiation, which is major part of preparative regimen for BMT, affect endocrine function, subsequent growth, gonadal function, development of secondary malignancies. We propose the indication of TBI for children and young adults as follows; those who are at high risk for leukemic relapse after BMT such as Phl-positive-All, leukemia-lymphoma syndrome, AML with monocytic component, BMT in elapse, BMT from other than HLA-matched siblings. (author)

  12. Cytogenetic and morphological assessment of bone marrow in therapeutic irradiation

    International Nuclear Information System (INIS)

    Sharma, U.; Das, B.P.; Singhal, R.M.; Radhakrishnaiah, Y.; Rath, G.K.; Padmaraju, I.; Bhargava, V.L.

    1978-01-01

    Morphological and cytogenetic study from the irradiated bone marrow, in 59 cases of radically irradiated carcinoma cervix was done. Regeneration of a marrow adjudged on cellular morphology was after 12 months whereas cytogenetic studies revealed it at the end of three months. It is concluded that cytogenetic study is a more sensitive parameter in assessing the recovery of bone marrow. (author)

  13. Blastema from rabbit ear contains progenitor cells comparable to marrow derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Mohamadreza Baghaban Eslaminejad

    2012-09-01

    Full Text Available Rabbits have the capacity to regenerate holes in their ears by forming a blastema, a tissue that is made up of a group of undifferentiated cells. The purpose of the present study was to isolate and characterize blastema progenitor cells and compare them with marrow mesenchymal stem cells (MSCs. Five New Zealand white male rabbits were used in the present study. A 2-mm hole was created in the animal ears. After 4 days, the blastema ring formed in the periphery of the hole was removed and cultivated. The cells were expanded through several subcultures and compared with the MSCs derived from the marrow of same animal in terms of in vitro differentiation capacity, growth kinetics and culture requirements for optimal proliferation. The primary cultures from both cells tended to be heterogeneous. Fibroblastic cells became progressively dominant with advancing passages. Similar to MSCs blastema passaged-3 cells succeeded to differentiate into bone, cartilage and adipose cell lineages. Even lineage specific genes tended to express in higher level in blastema cells compared to MSCs (p < 0.05. Moreover blastema cells appeared more proliferative; producing more colonies (p < 0.05. While blastema cells showed extensive proliferation in 15% fetal bovine serum (FBS, MSCs displayed higher expansion rate at 10% FBS. In conclusion, blastema from rabbit ear contains a population of fibroblastic cells much similar in characteristic to bone marrow mesenchymal stem cells. However, the two cells were different in the level of lineage-specific gene expression, the growth curve characteristics and the culture requirements.

  14. Allogeneic bone marrow grafts in genotyped swine

    International Nuclear Information System (INIS)

    Vaiman, M.

    1974-01-01

    The proof of a major histocompatibility complex (MHC) called SL-A enabled to promote bone marrow allografts. A study of the response to that kind of graft in irradiated pig states a number of interesting points. Bone marrow allografting complies with the rule of tissular compatibility with the major histocompatibility complex. The taking of SL-A incompatible bone marrow allografts could not be achieved under the experimental conditions. In spite of the high doses of radiation, 950 to 1050 rads, higher than 1.5 LD 100%, recipients were capable of rejecting their grafts, regularly. SL-A identify ensured 100%, initial achievement. However, animals developed regular fatal disease within a fairly short time. This development could by no means, be ascribed to the sole sequealae of radiation sickness since autografted animals at equal or even higher doses, showed none of the symptome. Assumption of a chronic graft-vs-host reactions, induced by the minor histocompatible systems, was put foreward, but should be confirmed histopathologically [fr

  15. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

    1982-01-01

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

  16. Psychiatric disorders in bone marrow transplant patients

    International Nuclear Information System (INIS)

    Khan, A.G.; Irfan, M.; Shamsi, T.S.; Hussain, M.

    2007-01-01

    To identify the psychiatric illnesses in patients with hematological/oncological disorders encountered during blood and bone marrow transplantation. All consecutive patients, aged 15 years and above, who fulfilled inclusion and exclusion criteria and underwent blood and bone marrow transplantation, were enrolled in this study. Psychiatric assessment comprised of a semi-structured interview based on Present Status Examination (PSE). The psychiatric diagnosis was made on the basis of International Classification of Diseases (ICD-10) system of classification devised by W.H.O. Eighty patients, who fulfilled the inclusion criteria, were inducted in this study. Thirty (37.5%) cases were found to have psychiatric disorders. Out of the total, 60 (75%) were males and 20 (25%) females. Adjustment disorder was the most frequent diagnosis (n=12), followed by major depression (n=7). Rest of the diagnoses made were generalized anxiety disorder, acute psychotic disorder, delirium and depressive psychosis. High psychiatric morbidity associated with blood and bone marrow transplantation was observed. It indicates the importance of psychiatric intervention during the isolation period of BMT as well as pre-transplant psychiatric assessment and counseling regarding procedure. (author)

  17. Methods of bone marrow dose calculation

    International Nuclear Information System (INIS)

    Taboaco, R.C.

    1982-02-01

    Several methods of bone marrow dose calculation for photon irradiation were analised. After a critical analysis, the author proposes the adoption, by the Instituto de Radioprotecao e Dosimetria/CNEN, of Rosenstein's method for dose calculations in Radiodiagnostic examinations and Kramer's method in case of occupational irradiation. It was verified by Eckerman and Simpson that for monoenergetic gamma emitters uniformly distributed within the bone mineral of the skeleton the dose in the bone surface can be several times higher than dose in skeleton. In this way, is also proposed the Calculation of tissue-air ratios for bone surfaces in some irradiation geometries and photon energies to be included in the Rosenstein's method for organ dose calculation in Radiodiagnostic examinations. (Author) [pt

  18. Radionuclide imaging of bone marrow in hematologic systemic disease

    Energy Technology Data Exchange (ETDEWEB)

    Kessel, F.; Hahn, K.; Gamm, H.

    1987-02-01

    Radionuclide imaging studies of the bone marrow were carried out in 164 patients suffering from hematologic systemic disease. One third of 90 patients with Hodgkin lymphoma (HL) or Non Hodgkin lymphoma (NHL) displayed a pathological distribution pattern representing bone marrow expansion. In HL there were 17% accumulation defects caused by metastases in contrast to only 7% in NHL. Among 30 patients with chronic myelocytic leukemia bone marrow expansion was found in 60%, bone marrow displacement and aplasia 10%. Focal bone marrow defects were found in 3 patients. All patients with primary polycythemia rubra vera displayed a pathologic bone marrow distribution pattern as well as splenomegaly. All patients with acute myelocytic leukemia (AML) and one patient with an acute lymphatic leukemia (ALL) had a pathological distribution pattern with bone marrow expansion and displacement. Focal bone marrow defects were not seen. Multiple myeloma with bone marrow expansion was found in 6 of 12 patients and focal accumulation defects were found in 40%, the latter lesions being not visible or equivocal on skeletal imaging studies. Pathological changes in liver and spleen were found in a high percentage of the total collective. The results document the important clinical value of bone marrow scintigraphy among the hematologic diseases studied.

  19. Meeting report of the 2016 bone marrow adiposity meeting.

    Science.gov (United States)

    van der Eerden, Bram; van Wijnen, André

    2017-10-02

    There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies.

  20. Central and peripheral distribution of bone marrow on bone marrow scintigraphy with antigranulocytic antibody in hematologic malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young [Dong-A University College of Medicne, Busan (Korea, Republic of); Lee, Jae Tae; Sohn, Sang Kyun; Lee, Kyu Bo [Kyungpook National University School of Medicine, Taegu (Korea, Republic of)

    2002-10-01

    Bone marrow scintigraphy has been used to evaluate the status of bone marrow in various hematologic disorders. We have analyzed the peripheral distribution pattern and central uptake ratio of bone marrow using anti-NCA-95 monoclonal antibody and the their correlation in patients with various hematologic malignancy. Bone marrow immunoscintigraphy was performed using Tc-99m anti-granulocyte monoclonal mouse antibody BW 250/183. Fifty patients were classified into four groups; 11 with acute myelogenous leukemia, 12 with acute lymphocytic leukemia, 15 with lymphoma and 12 with myelodysplastic syndrome. Th extension of peripheral bone marrow was categorized into four grades: I, II, III and IV. The activity of central bone marrow was expressed as sacroiliac uptake ratio. The patient's number was 4 in grade I, 27 in grade II, 15 in grade III and 4 in grade IV according to extension of peripheral bone marrow. The extension of peripheral bone marrow was marked (58% in grade III and IV) in myelodysplastic syndrome and acute lymphocytic leukemia and mild (93% in grade I and II) in lymphoma. Sacroiliac uptake ratio was highest (8.5{+-}4.0) in myelodysplastic syndrome and lowest (5.9{+-}3.6) in acute myelogenous leukemia, but not significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). Sacroiliac uptake ratio of whole patients was significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). The pattern of peripheral bone marrow extension and activity of central hemopoietic marrow were not specific to the disease entities. Response of hemopoietic bone marrow may be evaluated on both peripheral and central bone marrow in patients with hematologic malignancy.

  1. Central and peripheral distribution of bone marrow on bone marrow scintigraphy with antigranulocytic antibody in hematologic malignancy

    International Nuclear Information System (INIS)

    Kang, Do Young; Lee, Jae Tae; Sohn, Sang Kyun; Lee, Kyu Bo

    2002-01-01

    Bone marrow scintigraphy has been used to evaluate the status of bone marrow in various hematologic disorders. We have analyzed the peripheral distribution pattern and central uptake ratio of bone marrow using anti-NCA-95 monoclonal antibody and the their correlation in patients with various hematologic malignancy. Bone marrow immunoscintigraphy was performed using Tc-99m anti-granulocyte monoclonal mouse antibody BW 250/183. Fifty patients were classified into four groups; 11 with acute myelogenous leukemia, 12 with acute lymphocytic leukemia, 15 with lymphoma and 12 with myelodysplastic syndrome. Th extension of peripheral bone marrow was categorized into four grades: I, II, III and IV. The activity of central bone marrow was expressed as sacroiliac uptake ratio. The patient's number was 4 in grade I, 27 in grade II, 15 in grade III and 4 in grade IV according to extension of peripheral bone marrow. The extension of peripheral bone marrow was marked (58% in grade III and IV) in myelodysplastic syndrome and acute lymphocytic leukemia and mild (93% in grade I and II) in lymphoma. Sacroiliac uptake ratio was highest (8.5±4.0) in myelodysplastic syndrome and lowest (5.9±3.6) in acute myelogenous leukemia, but not significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). Sacroiliac uptake ratio of whole patients was significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). The pattern of peripheral bone marrow extension and activity of central hemopoietic marrow were not specific to the disease entities. Response of hemopoietic bone marrow may be evaluated on both peripheral and central bone marrow in patients with hematologic malignancy

  2. Magnetic resonance imaging of bone marrow disease in children

    International Nuclear Information System (INIS)

    Cohen, M.D.; Klatte, E.C.; Baehner, R.

    1984-01-01

    Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumors as well as CT. MRI showed marrow abnormality in four children who had leukemia

  3. Differentiation of bone marrow cells with irradiated bone in vitro

    International Nuclear Information System (INIS)

    Toshiyuki Tominaga; Moritoshi Itoman; Izumi, T.; Wakita, R.; Uchino, M.

    1999-01-01

    Disease transmission or infection is an important issue in bone allograft, and irradiation is used for sterilization of graft bones. One of the advantages of bone allograft over biomaterials is that graft bones have osteoinductive factors such as growth factors. Irradiation is reported to decrease the osteoinductive activity in vivo. We investigated the osteoinductive activity of irradiated bone by alkaline phosphatase (ALP) activity in rat bone marrow cell culture. Bones (tibias and femurs of 12-week-old Wistar rats) were cleaned of adhering soft tissue, and the marrow was removed by washing. The bones were defatted, lyophilized, and cut into uniform 70 mg fragments. Then the Bone fragments were irradiated at either 10, 20, 25, 30, 40, or 50 kGy at JAERI. Bone marrow cells were isolated from tibias and femurs of 4-week-old Wistar rats. Cells were plated in tissue culture flask. When primary cultures reached confluence, cells were passaged (4 x 103 cell / cm2) to 6 wells plates. The culture medium consisted of minimum essential medium, 10% fetal bovine serum, ascorbic acid, and antibiotics. At confluence, a cell culture insert was set in the well, and an irradiated bone fragment was placed in it. Then, medium was supplemented with 10 mM ?-glycerophosphate and 1 x 10-8 M dexamethasone. Culture wells were stained by naphthol AS-MX phosphate, N,N-dimethyl formamide, Red violet LB salt on day 0, 7, 14. The density of ALP staining was analyzed by a personal computer. Without bones, ALP staining increased by 50% on day 7 and by 100% on day 14, compared with that on day 0. The other side, with bones irradiated at 30 kGy or lower, ALP staining increased by 150% on day 7, and by 180% on day 14, compared with that on day 0. In the groups of irradiated bones of 40 kGy or higher, the increase in ALP staining was less prominent compared with the groups of irradiated bones of 30 kGy or lower. In the groups of 0-30 kGy irradiation, ALP staining increased in the early period

  4. Engineering bone grafts with enhanced bone marrow and native scaffolds.

    Science.gov (United States)

    Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

    2013-01-01

    The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. © 2013 S. Karger AG, Basel

  5. Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

    Science.gov (United States)

    Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

    2015-11-01

    Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Magnetic resonance imaging in diffuse malignant bone marrow diseases

    Energy Technology Data Exchange (ETDEWEB)

    Nyman, R.; Rehn, S.; Glimelius, B.; Hagberg, H.; Hemmingsson, A.; Jung, B.; Simonsson, B.; Sundstroem, C.

    Twenty-four patients with malignant bone marrow involvement or polycythemia vera, 8 patients with reactive bone marrow and 7 healthy individuals were examined with spin-echo magnetic resonance imaging at 0.35 T and 0.5 T. Signs of an increased longitudinal relaxation time, T1, were found when normal bone marrow was replaced by malignant cells, polycythemia vera or reactive marrow. A shortened T1 was indicated in 4 patients in bone marrow regions treated by radiation therapy; the marrow was most likely hypocellular in these cases. The estimated T1 relaxation times were highly correlated to the cellularity of the bone marrow as assessed by histology. Among patients with close to 100% cellularity neither T1 nor T2 discriminated between the various malignancies or between malignant and reactive, non-malignant bone marrow. Characterization of tissues in terms of normalized image intensities was also attempted, the motive being to avoid approximations and uncertainties in the assessment of T1 and T2. The normalization was carried out with respect to the image of highest intensity, i.e. the proton density weighted image. The results were in agreement with those for T1 and T2. It was concluded that MRI is valuable for assessing bone marrow cellularity, but not for differentiating between various bone marrow disorders having a similar degree of cellularity.

  7. Transplantation of bone marrow cells into lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Hermanova, E.

    1978-01-01

    Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

  8. Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

    1982-01-01

    A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

  9. Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

    Science.gov (United States)

    Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

    2017-06-01

    Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  10. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    International Nuclear Information System (INIS)

    Waksman, Ron; Baffour, Richard

    2003-01-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell

  11. Nuclear accidents and bone marrow graft

    International Nuclear Information System (INIS)

    Bernard, J.

    1988-01-01

    In case of serious contamination, the only efficacious treatment is the bone marrow grafts. The graft types and conditions have been explained. To restrict the nuclear accidents consequences, it is recommended to: - take osseous medulla of the personnel exposed to radiations and preserve it , that permits to carry out rapidly the auto-graft in case of accidents; - determine, beforehand, the HLA group of the personnel; - to register the voluntary donors names and addresses, and their HLA group, that permits to find easily a compatible donar in case of allo-graft. (author)

  12. Successful bone marrow transplantation in sensitized recipients

    International Nuclear Information System (INIS)

    Levey, R.H.; Parkman, J.; Rappeport, J.; Nathan, D.G.; Rosen, F.

    1979-01-01

    Fourteen patients with aplastic anemia and one with the Wiskott-Aldrich syndrome who were specifically sensitized against their donors were successfully engrafted with bone marrow from those donors. Sensitivity was detected in antibody-independent and antibody-dependent cell-mediated lysis assays. In order to erase this immunity to non-MHR familial transplantation antigens, multiagent immunosuppression with cyclophosphamide, procarbazine, and whole rabbit antithymocyte serum (ATS) was used. The data suggest that ATS was largely responsible for abrogation of this sensitivity and indicate that immunity does not represent a barrier to successful transplantation

  13. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis.

    Science.gov (United States)

    Fairfield, Heather; Falank, Carolyne; Harris, Elizabeth; Demambro, Victoria; McDonald, Michelle; Pettitt, Jessica A; Mohanty, Sindhu T; Croucher, Peter; Kramer, Ina; Kneissel, Michaela; Rosen, Clifford J; Reagan, Michaela R

    2018-02-01

    The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers. Herein we provide evidence that signals from the bone matrix (osteocytes) determine marrow adiposity by regulating adipogenesis in the bone marrow. Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce adipogenesis in 3T3-L1 cells, mouse ear- and BM-derived MSCs, and human BM-derived MSCs. We demonstrate that the mechanism of SOST induction of adipogenesis is through inhibition of Wnt signaling in pre-adipocytes. We also demonstrate that a decrease of sclerostin in vivo, via both genetic and pharmaceutical methods, significantly decreases bone marrow adipose tissue (BMAT) formation. Overall, this work demonstrates a direct role for SOST in regulating fate determination of BM-adipocyte progenitors. This provides a novel mechanism for which BMAT is governed by the local bone microenvironment, which may prove relevant in the pathogenesis of certain diseases involving marrow adipose. Importantly, with anti-sclerostin therapy at the forefront of osteoporosis treatment and a greater recognition of the role of BMAT in disease, these data are likely to have important clinical implications. © 2017 Wiley Periodicals, Inc.

  14. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.

    Science.gov (United States)

    Reyes, M; Lund, T; Lenvik, T; Aguiar, D; Koodie, L; Verfaillie, C M

    2001-11-01

    It is here reported that mesenchymal stem cells known to give rise to limb-bud mesoderm can, at the single-cell level, also differentiate into cells of visceral mesoderm and can be expanded extensively by means of clinically applicable methods. These cells were named mesodermal progenitor cells (MPCs). MPCs were selected by depleting bone marrow mononuclear cells from more than 30 healthy human donors of CD45(+)/glycophorin-A (GlyA)(+) cells. Cells were cultured on fibronectin with epidermal growth factor and platelet-derived growth factor BB and 2% or less fetal calf serum. It was found that 1/5 x 10(3) CD45(-)GlyA(-) cells, or 1/10(6) bone marrow mononuclear cells, gave rise to clusters of small adherent cells. Cell-doubling time was 48 to 72 hours, and cells have been expanded in culture for more than 60 cell doublings. MPCs are CD34(-), CD44(low), CD45(-), CD117 (cKit)(-), class I-HLA(-), and HLA-DR(-). MPCs differentiated into cells of limb-bud mesoderm (osteoblasts, chondrocytes, adipocytes, stroma cells, and skeletal myoblasts) as well as visceral mesoderm (endothelial cells). Retroviral marking was used to definitively prove that single MPCs can differentiate into cells of limb bud and visceral mesoderm. Thus, MPCs that proliferate without obvious senescence under clinically applicable conditions and differentiate at the single-cell level not only into mesenchymal cells but also cells of visceral mesoderm may be an ideal source of stem cells for treatment of genetic or degenerative disorders affecting cells of mesodermal origin.

  15. Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation.

    Science.gov (United States)

    Hisatomi, Toshio; Sonoda, Koh-hei; Ishikawa, Fumihiko; Qiao, Hong; Nakazawa, Takahiro; Fukata, Mitsuhiro; Nakamura, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi-Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

    2007-04-01

    To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU.

  16. The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

    International Nuclear Information System (INIS)

    Tabak, Daniel

    1997-01-01

    This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

  17. β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

    Science.gov (United States)

    Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

    2017-12-01

    Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells

    Science.gov (United States)

    Bowser, Matthew; Herberg, Samuel; Arounleut, Phonepasong; Shi, Xingming; Fulzele, Sadanand; Hill, William D.; Isales, Carlos M.; Hamrick, Mark W.

    2013-01-01

    The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin: follistatin ratio increased significantly (+75%) in mouse bone marrow with age, as did activin A levels (+17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice. PMID:23178301

  19. New experimental approach to treatment of radiation-induced bone marrow aplasia: ex vivo expansion of hematopoietic cells

    International Nuclear Information System (INIS)

    Herodin, F.; Mathieu, J.; Drouet, M.; Grenier, N.; Grange, L.; Bourin, P.; Vetillard, J.; Thierry, D.; Mestries, J.C.

    1995-01-01

    The management of bone marrow aplasia secondary to accidental exposure to high doses of ionizing radiations requires new therapeutic protocols in addition to cytokine therapy. The in vitro incubation of hematopoietic stem and progenitor cells from irradiated nonhuman primates with negative and positive regulators of hematopoiesis may lead to helpful products of transfusion. (author)

  20. Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

    Science.gov (United States)

    Domaratskaya, E.; Starostin, V.

    The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations

  1. Connective Tissue Growth Factor reporter mice label a subpopulation of mesenchymal progenitor cells that reside in the trabecular bone region.

    Science.gov (United States)

    Wang, Wen; Strecker, Sara; Liu, Yaling; Wang, Liping; Assanah, Fayekah; Smith, Spenser; Maye, Peter

    2015-02-01

    Few gene markers selectively identify mesenchymal progenitor cells inside the bone marrow. We have investigated a cell population located in the mouse bone marrow labeled by Connective Tissue Growth Factor reporter expression (CTGF-EGFP). Bone marrow flushed from CTGF reporter mice yielded an EGFP+ stromal cell population. Interestingly, the percentage of stromal cells retaining CTGF reporter expression decreased with age in vivo and was half the frequency in females compared to males. In culture, CTGF reporter expression and endogenous CTGF expression marked the same cell types as those labeled using Twist2-Cre and Osterix-Cre fate mapping approaches, which previously had been shown to identify mesenchymal progenitors in vitro. Consistent with this past work, sorted CTGF+ cells displayed an ability to differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and into osteoblast, adipocyte, and stromal cell lineages after transplantation into a parietal bone defect. In vivo examination of CTGF reporter expression in bone tissue sections revealed that it marked cells highly localized to the trabecular bone region and was not expressed in the perichondrium or periosteum. Mesenchymal cells retaining high CTGF reporter expression were adjacent to, but distinct from mature osteoblasts lining bone surfaces and endothelial cells forming the vascular sinuses. Comparison of CTGF and Osterix reporter expression in bone tissue sections indicated an inverse correlation between the strength of CTGF expression and osteoblast maturation. Down-regulation of CTGF reporter expression also occurred during in vitro osteogenic differentiation. Collectively, our studies indicate that CTGF reporter mice selectively identify a subpopulation of bone marrow mesenchymal progenitor cells that reside in the trabecular bone region. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Bone marrow scintigraphy with 111In-chloride

    International Nuclear Information System (INIS)

    Kan, Masayasu; Miyamae, Tatsuya

    1977-01-01

    111 In-chloride as a useful bone marrow-scanning agent has been used for various hematological diseases. We also have studied the distribution of indium-111 by scintigraphy in 28 patients with systemic hematopoietic disorders and other: 4 with aplastic anemia, 8 with leucemia, 3 with iron-deficiency anemia, one with pernicious anemia, 2 with myelofibrosis, 3 with multiple myeloma, one with malignant lymphoma, 3 with liver cirrhosis or Banti-syndrome and 3 with seminoma received post operative irradiation. The results of scintigraphy (the image of bone marrow, liver, spleen, kidney and intestine) were compared with bone marrow biopsies, ferrokinetic data and Se.I./TIBC. The bone marrow image was interpreted on a three-point scale: normal distribution of activity (+), abnormal distribution (+-), body back ground level (-). In the cases of iron-deficiency anemia and pernicious anemia with hyperplastic erythroid marrow, regardless of its severe anemia, the scintigrams showed clearly delineated bone marrow images and normal organ distribution of indium. On the other hand, the scan images revealed severe suppressions of bone marrow activity and markedly increased renal activity in some cases of aplastic anemia, acute leucemia and malignant lymphoma with hypoplastic and/or tumour-cell infiltrative marrows. Thus, it may be said that the bone marrow uptake of indium-111 correlates well with the degree of erythroid elements, no correlation with nucleated cell counts, and there is a strong tendency to increased renal activity in the cases of markedly decreased erythropoietic cell counts. (auth.)

  3. Recent progress in the differentiation of bone marrow derived ...

    African Journals Online (AJOL)

    Bone marrow mesenchymal stem cells (BMMSCs) are one of the cells found in bone marrow stromal. A large number of studies have shown that BMMSCs cannot only differentiate into hematopoietic stromal cells, but can migrate and position themselves in multiple non-hematopoietic organizations and differentiate into the ...

  4. Magnetic resonance in hematological diseases. Imaging of bone marrow

    DEFF Research Database (Denmark)

    Jensen, K.E.

    1995-01-01

    Magnetic resonance imaging (MRI) is a highly sensitive alternative to plain radiography, CT, and radionuclide studies for the imaging of normal and abnormal bone marrow. The cellularity and the corresponding fat/water ratio within the bone marrow show clear changes in haematological diseases. Thi...

  5. Bone Marrow Edema: An MRI Diagnostic Clue in Patients with ...

    African Journals Online (AJOL)

    Results: bone marrow edema intrinsic to osseous lesions were noted in 22 patients. Bone marrow edema with associated soft tissue lesions were noted in 25 patients findings included tenosynovitis in 15, impingement syndromes in seven diabetic foot infection in two and diabetic osteoneuroarthropathy in one patient .

  6. Bone marrow stromal cell : mediated neuroprotection for spinal cord repair

    NARCIS (Netherlands)

    Ritfeld, Gaby Jane

    2014-01-01

    Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic

  7. Recent progress in the differentiation of bone marrow derived ...

    African Journals Online (AJOL)

    ONOS

    2010-08-09

    Aug 9, 2010 ... Bone marrow mesenchymal stem cells (BMMSCs) are one of the cells found in bone marrow stromal. A large number of ..... BMMSCs and myocardial cells using biomimetic electrical ... effect ventricular remodeling after infarction. Meyern et al. ... to small sample sizes and different experimental con- ditions.

  8. Bone marrow and chelatable iron in patients with protein energy ...

    African Journals Online (AJOL)

    Objectives: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. Design: Bone marrow iron was assessed histologicaHy in ...

  9. Bone marrow transplantations to study gene function in hematopoietic cells

    NARCIS (Netherlands)

    de Winther, Menno P. J.; Heeringa, Peter

    2011-01-01

    Immune cells are derived from hematopoietic stem cells in the bone marrow. Experimental replacement of bone marrow offers the unique possibility to replace immune cells, to study gene function in mouse models of disease. Over the past decades, this technique has been used extensively to study, for

  10. Bone-marrow MR imaging before and after autologous marrow transplantation in lymphoma patients without known bone-marrow involvement

    International Nuclear Information System (INIS)

    Lien, H.H.; Blomlie, V.; Blystad, A.K.; Holte, H.; Kvaloey, S.; Langholm, R.

    1997-01-01

    Purpose: To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. appearances that could simulate tumor. Material and Methods: Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images. Results: T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p<0.01, Student's t-test, 2-sided test). Conclusion: Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years. (orig.)

  11. Regulated proliferation of primitive hematopoietic progenitor cells in long-term human marrow cultures

    International Nuclear Information System (INIS)

    Cashman, J.; Eaves, A.C.; Eaves, C.J.

    1985-01-01

    We have examined the cycling status of various classes of erythroid and granulopoietic progenitor populations maintained for many weeks in standard normal long-term human marrow cultures. These were initiated with a single inoculum of marrow aspirate and were routinely fed by weekly removal of half of the nonadherent cells and replacement of half of the growth medium. Progenitors of large erythroid colonies (more than eight erythroblast clusters) present in the nonadherent fraction and progenitors of small granulocyte/macrophage colonies (fewer than 500 cells) present in both the nonadherent and adherent fractions were found to be actively cycling at all times examined (28% to 63% kill following a 20-minute exposure to 20 microCi/mL of high specific activity 3 H-thymidine). In contrast, progenitors of large granulocyte/macrophage colonies (more than 500 cells) and progenitors of large erythroid colonies (more than eight erythroblast clusters), present in the adherent layer, consistently alternated between a quiescent state at the time of each weekly medium change and a proliferating state two to three days later (0% to 13% kill and 21% to 49% kill, respectively). Additional experiments revealed that the activation of primitive progenitors in the adherent layer was not dependent on the addition of fresh glutamine or hydrocortisone, nor on the physical manipulations involved in changing the growth medium. These studies provide the first direct evidence that normal long-term human marrow cultures support the continued turnover of a variety of early hematopoietic progenitor cell types. Further, they indicate that the proliferative activity of the most primitive of these progenitors is regulated by stage-specific cell-cell interactions that are subject to manipulation

  12. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    Science.gov (United States)

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Bone marrow scintigraphy with antigranulocyte antibody in multiple myeloma: comparison with simple radiography and bone scintigraphy

    International Nuclear Information System (INIS)

    Kim, Dong Hwan; Lee, Jae Tae; Baek, Jin Ho

    1998-01-01

    Simple X-ray study and bone scan have limitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow immunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement in multiple myeloma. In 22 patients (Male: 15, Female: 7) with multiple myeloma, we performed whole-body immunoscintigraphy using 99m Tc-labelled antigranulocyte antibody (BW 250/183, Scintimum Granulozyt R CIS, France) and compared the findings with those of simple bone radiography and 99m Tc-MDP bone scan. Abnormal findings in bone marrow scintigraphy were considered to be present in case of expansion of peripheral bone marrow or focal photon defect in axial bones. Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone marrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiogrpahy (58 sites, 47%) or bone scan (40 sites, 32%). Fifty-one(41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Bone marrow scan using 99m Tc-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray or bone scan in patients with multiple myeloma

  14. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  15. Red-yellow marrow conversion: Its effect on the location of some solitary bone lesions

    International Nuclear Information System (INIS)

    Kricun, M.E.

    1985-01-01

    The location of red marrow related bone lesions is dependent upon the distribution of red marrow. It is altered by the normal conversion of red marrow to yellow (fat) marrow and by the reconversion of yellow marrow to red marrow caused by marrow infiltrating disorders or marrow stress disorders. (orig.)

  16. Detection of bone marrow involvement in patients with cancer

    International Nuclear Information System (INIS)

    Federico, M.; Silingardi, V.; Wright, R.M.

    1989-01-01

    Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is alredy the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow

  17. Bone Marrow and Peripheral Blood Leptin Levels in Lymphoproliferative Diseases - Relation to the Bone Marrow Fat and Infiltration

    Czech Academy of Sciences Publication Activity Database

    Gaja, A.; Churý, Z.; Pecen, Ladislav; Fraňková, H.; Jandáková, H.; Hejlová, N.

    2000-01-01

    Roč. 47, č. 5 (2000), s. 307-312 ISSN 0028-2685 Institutional research plan: AV0Z1030915 Keywords : leptin * bone marrow fat * bone marrow infiltration * lymphoproliferative disease Subject RIV: BA - General Mathematics Impact factor: 0.579, year: 2000

  18. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

    Science.gov (United States)

    Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

    2015-03-13

    Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

  19. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 1

    International Nuclear Information System (INIS)

    Fujimori, Katsuhiko

    1976-01-01

    In 42 patients with hypoplastic anemia, 10 mCi of sup(99m)Tc sulfur colloid was injected intravenously, and scanning was performed one hour later with a Pho/Gamma III scintillation camera. Active bone marrow was usually found in the sternum, vertebrae, pelvis, and the poximal ends of humeri and femurs. These 42 cases were classified into 5 types according to distribution pattern. Type 1 (4 cases) showed complete lack of sup(99m)Tc activity in the usual marrow sites. Ferrokinetic studies indicated remarkable erythropoietic hypofunction. Type 2 (18 cases) showed island-like distribution of marrow in the pelvis or in the heads of humeri and femurs. Type 3 (6 cases) showed approximately normal uptake of sup(99m)Tc sulfur colloid in the sternum and the vertebrae, but no activity in the pelvis; or showed the apposite distribution. Marrow specimens obtained from the sternum and the pelvis showed differences in cellularity in such cases. Type 4 (8 cases) were divided into two groups, A and B. Four patients of group A showed decreased uptake of the colloid in the usual marrow sites, but expanded marrow extending into distal femous, proximal and distal tibiae and bones of the feet. These patients subsequently developed leukemia. The diagnosis was confirmed at autopsy or when leukemic features appeared during the clinical course. The remaining cases, group B, showed island-like sup(99m)Tc activity in the tibia. Until then, there had been no signs of leukemia. Type 5 (6 cases) showed normal distribution with below-normal uptake. It is concluded that the reduction of hematopoietic tissue mass is the main cause of decreased hematopoiesis in hypoplastic anemia. (J.P.N.)

  20. Diabetes mellitus induces bone marrow microangiopathy

    Science.gov (United States)

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P.J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Objective The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and results We found profound structural alterations in BM from type-1 diabetic mice, with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32pos endothelial cells (ECs). Cultured ECs from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker β-galactosidase, reduced migratory and network-formation capacities and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineageneg c-Kitpos Sca-1pos (LSK) cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes LSK cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage and activation of apoptosis. Boosting the anti-oxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion and LSK cell depletion. Conclusions We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM. These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes. PMID:20042708

  1. Colonic complications following human bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paulino Martínez Hernández-Magro

    2015-01-01

    Full Text Available Background: Human bone marrow transplantation (BMT becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. Objective: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD, and treatment of patients suffering with colonic complications of human bone marrow transplantation. Patients and methods: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. Results: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%; five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%; graft vs. host disease was present in 16 patients (20%; 13 patients (16.8% developed acute colonic GVHD, and 3 (3.8% chronic GVHD. Infection was identified in 9 patients (11.6%. Conclusions: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0–20 day chemotherapy toxicity, 20 and more GVHD, and infection could appear in any time of transplantation. Resumo: Experiência: O transplante de medula óssea humana (MOH passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. Objetivo: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto

  2. Transient Bone Marrow Edema Syndrome (Case Report

    Directory of Open Access Journals (Sweden)

    Nilnur Konuralp

    2003-09-01

    Full Text Available Transient bone marrow edema syndrome (BMES is accepted as a possible cause of acute disabling hip pain. This syndrome is defined as local osteoporosis in hip in radiographies, BME in MRI which can be rarely seen and has a self-limiting course. Although the disease generally has a self-limiting course, surgical treatment by early core decompression of the femoral head has proven effective in rapidly relieving the symptoms. Although BMES is relatively rare and probably underdiagnosed when compared to nontraumatic osteonecrosis, both conditions are associated with known osteonecrosis risk factors in middle aged men and especially with late (thirdhad trimester pregnancy in women. We have reported three cases with BMES that had different etiology and followed up presented the differential diagnosis to nontraumatic avascular osteonecrosis. These three cases were treated in early stage very succesfully.

  3. Hemolytic uremic syndrome after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Ayako; Sakamaki, Hisashi; Tanikawa, Shu [Tokyo Metropolitan Komagome Hospital (Japan)] [and others

    1998-06-01

    One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin`s lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient. (author)

  4. Good manufacturing practice-compliant expansion of marrow-derived stem and progenitor cells for cell therapy.

    Science.gov (United States)

    Gastens, Martin H; Goltry, Kristin; Prohaska, Wolfgang; Tschöpe, Diethelm; Stratmann, Bernd; Lammers, Dirk; Kirana, Stanley; Götting, Christian; Kleesiek, Knut

    2007-01-01

    Ex vivo expansion is being used to increase the number of stem and progenitor cells for autologous cell therapy. Initiation of pivotal clinical trials testing the efficacy of these cells for tissue repair has been hampered by the challenge of assuring safe and high-quality cell production. A strategy is described here for clinical-scale expansion of bone marrow (BM)-derived stem cells within a mixed cell population in a completely closed process from cell collection through postculture processing using sterile connectable devices. Human BM mononuclear cells (BMMNC) were isolated, cultured for 12 days, and washed postharvest using either standard open procedures in laminar flow hoods or using automated closed systems. Conditions for these studies were similar to long-term BM cultures in which hematopoietic and stromal components are cultured together. Expansion of marrow-derived stem and progenitor cells was then assessed. Cell yield, number of colony forming units (CFU), phenotype, stability, and multilineage differentiation capacity were compared from the single pass perfusion bioreactor and standard flask cultures. Purification of BMMNC using a closed Ficoll gradient process led to depletion of 98% erythrocytes and 87% granulocytes, compared to 100% and 70%, respectively, for manual processing. After closed system culture, mesenchymal progenitors, measured as CD105+CD166+CD14-CD45- and fibroblastic CFU, expanded 317- and 364-fold, respectively, while CD34+ hematopoietic progenitors were depleted 10-fold compared to starting BMMNC. Cultured cells exhibited multilineage differentiation by displaying adipogenic, osteogenic, and endothelial characteristics in vitro. No significant difference was observed between manual and bioreactor cultures. Automated culture and washing of the cell product resulted in 181 x 10(6) total cells that were viable and contained fibroblastic CFU for at least 24 h of storage. A combination of closed, automated technologies enabled

  5. Using Proteomics to 1) Identify the Bone Marrow Homing Receptors Expressed on Human Hematopoietic Stem Cells and 2) Elucidate Critical Signaling Pathways Responsible for the Blockage of Hematopoietic Differentiation in Leukemia

    KAUST Repository

    Chin, Chee J.

    2011-01-01

    Successful hematopoiesis requires the trafficking of hematopoietic stem/progenitor cells (HSPCs) to their bone marrow (BM) niche, where they can differentiate to produce all blood lineages. Leukemia arises when there is a blockage of differentiation

  6. A method for generation of bone marrow-derived macrophages from cryopreserved mouse bone marrow cells.

    Directory of Open Access Journals (Sweden)

    Fernanda M Marim

    Full Text Available The broad use of transgenic and gene-targeted mice has established bone marrow-derived macrophages (BMDM as important mammalian host cells for investigation of the macrophages biology. Over the last decade, extensive research has been done to determine how to freeze and store viable hematopoietic human cells; however, there is no information regarding generation of BMDM from frozen murine bone marrow (BM cells. Here, we establish a highly efficient protocol to freeze murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain their potential for BMDM differentiation for more than 6 years. We compared BMDM obtained from fresh and frozen BM cells and found that both are similarly able to trigger the expression of CD80 and CD86 in response to LPS or infection with the intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from fresh or frozen BM cells equally restrict or support the intracellular multiplication of pathogens such as L. pneumophila and the protozoan parasite Leishmania (L. amazonensis. Although further investigation are required to support the use of the method for generation of dendritic cells, preliminary experiments indicate that bone marrow-derived dendritic cells can also be generated from cryopreserved BM cells. Overall, the method described and validated herein represents a technical advance as it allows ready and easy generation of BMDM from a stock of frozen BM cells.

  7. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  8. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

    Directory of Open Access Journals (Sweden)

    William P Lafuse

    Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

  9. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 3. The bone marrow scintigraphy with /sup 111/In-chloride

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

    1976-04-01

    A study was made to determine wheter or not bone marrow scintigraphy with /sup 111/In chloride delineates the real distribution of hematopoietic cells. In a patient with acute myelogenous luekemia at the stage of complete remission, there was a significant incorporation of /sup 111/In into bone marrow cells (20 - 28% compared with 6% in the controls). Incorporation of /sup 111/In into peripheral blood cells was 0 at after 10 hours and 5% to 6% after 7 days. The plasma disappearance curve of /sup 111/In consisted of 2 exponential components, one with a half-life of 6.5 to 9.5 hours followed by a slow component with a half-life of 20 to 30 hours. 5 to 7% of the injected dose was excreted in the urine in 24 hours. The distribution of active marrow was investigated with bone marrow scintigraphy in various hematological disorders and the results were compared with those obtained with sup(99m)Tc sulfur colloid. The results obtained in this study suggest that /sup 111/In is incorporated into erythroid precursors, and that this property of /sup 111/In makes in an ideal bone marrow scanning agent for observation of real hematopoietic bone marrow distribution in blood disease.

  10. Assessment of functional displacement of bone marrow by osteoplastic metastases from prostatic carcinoma with bone marrow scintigraphy

    International Nuclear Information System (INIS)

    Venz, S.; Cordes, M.; Friedrichs, R.; Hosten, N.; Neumann, K.; Langer, R.; Nagel, R.; Felix, R.

    1993-01-01

    The detailed examination of the skeleton in prostate cancer has become more critical since surgical treatment requires the non-evidence of bone metastases. The data of 30 patients have been evaluated. All patients had a bone scan and a bone marrow scintigraphy with [ 99m Tc[-anti-NCA95. In this study we compared the degree of bone marrow displacement with the extent of metastatic deposits identified on the bone scan. Six patients showing the criterias of a superscan (maximal avidity of the osteotrope radiatracer) had as a correlate a complete displacement of the hematopoesis in the bone marrow scintigraphy and an increased activity in liver and spleen. The degree of the peripheral extension correlated strongly with the decrease of the haemoglobin in blood samples. The grading was based upon the number of metastatic deposits identified on the scan (0=no metastases; 1≤6 metastases; 2=multiple metastases; 3=superscan). In 28 of 30 patients (93%) we found corresponding results in both the bone scan and the bone marrow scintigraphy. The bone marrow scintigraphy is a sensitive method in the detection of metastatic disease and gives additional information about the extent of bone marrow displacement by osteoplastic metastases. (orig.) [de

  11. The usefulness of bone and bone-marrow scintigraphy in the detection of bone involvement in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Sone, Teruki

    1986-01-01

    We used a combination of bone and bone-marrow scintigraphy to evaluate bone involvement in 15 patients with multiple myeloma (7 in untreated group and 8 in chemotherapy group). Of the 3 cases in untreated group whose 99m Tc-methylene diphosphonate (MDP) bone scans showed no abnormality, one had abnormal 99m Tc-suffer colloid bone-marrow scintigraphy. In other 4 cases of untreated group whose bone scan showed cold defects, bone-marrow scintigraphy delineated clearly the areas of tumor-cell invasion. On the other hand, in all chemotherapy cases, multiple hot spots were observed on bone scintigram, but on bone-marrow scintigram abnormalities were not recognized. In conclusion, the combination scintigraphy of bone and bone-marrow was a useful method in evluating bone involvement in patients with multiple myeloma. (author)

  12. Iron overload following bone marrow transplantation in children: MR findings

    International Nuclear Information System (INIS)

    Kornreich, L.; Horev, G.; Grunebaum, M.; Yaniv, I.; Stein, J.; Zaizov, R.

    1997-01-01

    Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis. (orig.)

  13. Copper-64 labeled liposomes for imaging bone marrow

    International Nuclear Information System (INIS)

    Lee, Sang-gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar; Punzalan, Blesida; Larson, Steven M.; Pillarsetty, Naga Vara Kishore

    2016-01-01

    Introduction: Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [ 18 F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods: Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64 Cu incorporation into liposomes. Results: PET imaging and biodistribution studies with 64 Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69%ID/g for 90 nm liposomes and 7.01 ± 0.92%ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48%ID/g in tumor and 14.22 ± 8.07%ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49%ID/g and 2.23 ± 1.00%ID/g. Conclusion: Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents.

  14. Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study

    OpenAIRE

    Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

    2013-01-01

    Background Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. Methods MSCs were derived from negative ...

  15. Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM?) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

    OpenAIRE

    Angelini, Daniel J.; Su, Qingning; Kolosova, Irina A.; Fan, Chunling; Skinner, John T.; Yamaji-Kegan, Kazuyo; Collector, Michael; Sharkis, Saul J.; Johns, Roger A.

    2010-01-01

    Background Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling ...

  16. Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

    Science.gov (United States)

    Itkin, Tomer; Rafii, Shahin

    2017-09-11

    In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

  17. MR imaging of the bone marrow using short TI IR, 1. Normal and pathological intensity distribution of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Ishizaka, Hiroshi; Kurihara, Mikiko; Tomioka, Kuniaki; Kobayashi, Kanako; Sato, Noriko; Nagai, Teruo; Heshiki, Atsuko; Amanuma, Makoto; Mizuno, Hitomi.

    1989-02-01

    Normal vertebral bone marrow intensity distribution and its alteration in various anemias were evaluated on short TI IR sequences. Material consists of 73 individuals, 48 normals and 25 anemic patients excluding neoplastic conditions. All normal and reactive hypercellular bone marrow revealed characteristic intensity distribution; marginal high intensity and central low intensity, corresponding well to normal distribution of red and yellow marrows and their physiological or reactive conversion between red and yellow marrows. Aplastic anemia did not reveal normal intensity distribution, presumably due to autonomous condition.

  18. Bone marrow transplantation and other treatment after radiation injury

    International Nuclear Information System (INIS)

    Balner, H.

    1977-01-01

    This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

  19. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    International Nuclear Information System (INIS)

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-01-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically

  20. Bone marrow transplantation - a field in continuous development

    International Nuclear Information System (INIS)

    Pfeffer, P.F.

    1975-01-01

    The symptoms of the radiation syndrome are described briefly and the Vinca accident in 1958 is used as an illustration of the application of bone marrow transplantation as a treatment in radiation accidents. Thereafter the immunological problems arising when a permanent substitution of donor marrow is required are discussed. Greatest experience in bone marrow transplantation has been had in the treatment of aplastic anemia and acute leukemia. In these cases the recipient's bone marrow cells must be killed by whole body irradiation or by cyclophosphamide to preclude graft-host reaction. The removal of marrow from the donor and transplanting in the recipient are described, as is the progress of the patient in a typical case. The graft-host reaction is then discussed, as is the danger of secondary infections. In conclusion the long term results are evaluated and the future developments of the treatment discussed. (JIW)

  1. PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

    Directory of Open Access Journals (Sweden)

    Hiroto Iwasaki

    Full Text Available Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM cells, recent clinical trials have revealed less benefit from these therapies than expected.We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+/Lin(- (SL BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  2. The usefulness of measurement of whole body count in assessing bone marrow metastasis in cancer patients with increased periarticular bone uptake on follow-up bone scan: a comparison with bone marrow scan

    International Nuclear Information System (INIS)

    Jin, Seong Chan; Choi, Yun Young; Cho, Suk Shin

    2003-01-01

    Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung canner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases

  3. Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.

    Directory of Open Access Journals (Sweden)

    David F Razidlo

    2010-07-01

    Full Text Available Histone deacetylase (Hdac3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.

  4. Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

    Science.gov (United States)

    Eichler, Hermann; Orth, Patrick

    2017-01-01

    Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

  5. Bone marrow scintigraphy with 111In-chloride

    International Nuclear Information System (INIS)

    Aburano, Tamio; Ueno, Kyoichi; Sugihara, Masami; Tada, Akira; Tonami, Norihisa

    1977-01-01

    It is assumed that 111 In-chloride is bound to serum transferrin and then transported into reticulocyte in erythropoietic marrow. However, several biochemical differences between radioiron and 111 In have been reported since these years. In present study, clinical usefulness of 111 In-chloride bone marrow scintigraphy was examined especially by comparing 111 In-chloride image with sup(99m)Tc-colloid. Obtained results are as follows: 1) In most cases, both 111 In-chloride and sup(99m)Tc-colloid images showed similar bone marrow distributions. 2) In three out of 7 cases with hypoplastic anemia and two patients with bone marrow irradiation (700-1,000 rad), the central marrow or irradiated marrow showed marked decreased uptake of 111 In, and showed normal uptake of sup(99m)Tc. 3) In two out of 3 cases with chronic myelogenous leucemia, central marrow showed normal uptake of 111 In, and showed decreased uptake of sup(99m)Tc. From the present study, the same dissociation findings as those between radioiron and radiocolloid could be obtained in hypoplastic anemia and bone marrow irradiation. 111 In-chloride would appear to be a useful erythropoietic imaging agent, although further study of exact comparison with radioiron should be necessary. (auth.)

  6. Bone marrow examination findings at Aga Khan University Hospital ...

    African Journals Online (AJOL)

    Nutritional anaemia as a group was the most common haematological disorder ... examination in our patients with megaloblastic anaemia predominating. ... indication for bone marrow examination was anaemia followed by diagnostic work up ...

  7. Bone Marrow Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. 2nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams & Wilkins; c2014. Bone Marrow Aspiration and Biopsy; 99– ...

  8. Schwann cells promote neuronal differentiation of bone marrow ...

    African Journals Online (AJOL)

    Administrator

    2011-04-25

    Apr 25, 2011 ... Bone marrow stromal cells (BMSCs), a type of multipotent stem cell, can differentiate into various types ... induced to differentiate into neuron-like cells when they are ... axonal regeneration and functional reconstruction do not.

  9. Increased bone marrow blood flow in polycythemia vera

    International Nuclear Information System (INIS)

    Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

    1983-01-01

    Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a 133 Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple 133 Xe method may support the diagnosis of polycythemia vera. (orig.)

  10. Increased bone marrow blood flow in polycythemia vera

    Energy Technology Data Exchange (ETDEWEB)

    Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

    1983-01-01

    Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a /sup 133/Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple /sup 133/Xe method may support the diagnosis of polycythemia vera.

  11. Effect of some chemical radioprotectors on mouse bone marrow

    International Nuclear Information System (INIS)

    Lata, Manju; Ghose, A.; Khanna, C.M.

    1993-01-01

    Effect of 5-hydroxy-L-tryptophan (HT), AET and Se on mice bone marrow has been studied by counting bone marrow micronucleated cells and endogenous spleen colony count (CFU-S). Combination of HT and AET used as a radioprotector has not caused any significant variation in any of the parameter studied when administered once, it increases bone marrow micronucleated cells and decreases CFU-S slightly after daily administration for 7 days. The individual constituent of the combination administered singly does not increase micronucleated cell number. Seven consecutive doses of HT+AET and same in combination with Se enhances micronucleated cells to a higher level. Daily injection of Se alone up to 7 days also causes an increase in micronucleated cells up to same level. CFU-S pool does not show any significant change in number of bone marrow cells through out the study except in the groups where animals were treated with Se. (author). 15 refs., 3 tabs

  12. Hemopoiesis in bone marrow of lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Zoubkova, M.; Urbankova, J.

    1976-01-01

    A percentual representation of individual types of cells and their share of the restoration of hemopoiesis in bone marrow was observed on the 9th, 12th, 16th and 20th days following transplantation of bone marrow cells to letally irradiated mice. Myelopoiesis was ascertained which on the 20th day after transplantation became the dominant constituent and reached peak level around the 16th day after transplantation. The examination further showed that with regard to the period of irradiation and transplantation the erythropoiesis in bone marrow culminates on the 9th day after the transplantation and that normal values are quickly restored. On the 2ath day myelopoiesis and lymphopoiesis come close to values in normal bone marrow

  13. Regulation of glycogenesis in bone marrow of irradiated body

    Energy Technology Data Exchange (ETDEWEB)

    Barkalaya, A I

    1976-02-01

    In connection with a stimulating effect of insulin on postradiation restoration of medullary hemopoiesis the authors studied the influence of insulin on glycogenesis of bone marrow in comparison with glycogenesis of the liver under the conditions of irradiation. As a result the experiment made on white mice the authors established that the level of glycogen in both tissues on the first two days after irradiation (750 R) increased. Later, the decrease of glycogen concentration was observed and its exhaustion was more marked. Insulin protected bone marrow and the liver from exhaustion of glycogen reserves and ensured a higher level of glycogen in the liver. It is supposed that the regulation mechanisms by means of insulin of glycogenesis in the bone marrow and the liver are mainly of the same type. The influence of insulin on carbohydrate metabolism in the bone marrow is likely to be of significance for postradiation hemopoiesis.

  14. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)

    Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. PLN Kaparthi, G Namita, LK Chelluri, VSP Rao, PK Shah, A Vasantha, SK Ratnakar, K Ravindhranath ...

  15. Measurement of MC5 antibody distribution in blood and bone marrow

    International Nuclear Information System (INIS)

    Johnson, T.K.; Gonzales, R.; Kasliwal, R.; Lear, J.; Feyerabend, A.; Ceriani, R.; Bunn, P.

    1990-01-01

    PURPOSE: Bone marrow is most often the dose-limiting organ in radioimmunotherapy. Controversy exists over optimal methods of estimating dose exposure to bone marrow. The purpose of this paper is to compare bone marrow activity from serial blood samples versus bone marrow biopsy specimens as measures of dose exposure to bone marrow. Peripheral blood samples and bone marrow biopsy specimens were obtained at 48 and 168 hours after infusion from 12 female patients infused with iodine-131-labeled MC5 antibody. The percentage of bone marrow in each biopsy specimen was assumed to be equivalent to the percentage of active bone marrow estimated to be in the pelvis. Activity present in the bone marrow as calculated with use of the estimated bone marrow mass for an adult female and then compared with the peripheral blood activity

  16. Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes.

    Science.gov (United States)

    Espinoza, J Luis; Kotecha, Ritesh; Nakao, Shinji

    2017-01-01

    Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure.

  17. Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow

    International Nuclear Information System (INIS)

    Oyen, W.J.G.; Buijs, W.C.A.M.; Kampen, A. van; Koenders, E.B.; Claessens, R.A.M.J.; Corstens, F.H.M.

    1993-01-01

    Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq 111 In-labelled human polyclonal IgG ( 111 In-IgG) was administered 48h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48h after injection of 75 MBq 111 In-IgG. Bone marrow uptake in group 1 (4.5 ±1.3%D kg -1 ) was significantly lower than that in group 2 (8.5 ± 2.1%D kg -1 ) (P<0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low. (author)

  18. The usefulness of bone marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Morita, Rikushi

    1985-01-01

    A combination study of bone and bone marrow scintigraphy was performed on 25 pts with prostatic cancer, and, in order to study the usefulness in the diagnosis of bone metastasis, the findings of 2 scintigraphies were compared with those of skeletal roentgenography. Out of the 18 cases with the hot spots of sup(99m)Tc-MDP in the lower lumbar spine or/and the pelvic bone, 8 showed normal bone marrow scintigrams which were eventually proved to have degenerative changes of the spine accompanied by aging. On the other hand, nine cases of the ten, who had accumulation defects on the bone marrow scintigrams were finally proved having bone metastasis. All six cases with extensive bone metastases shown by bone scintigraphy with sup(99m)Tc-MDP, demonstrated multiple accumulation defects on bone marrow scintigraphy with sup(99m)Tc-sulfur colloid. In conclusion, bone marrow scintigraphy was thought to be helpful in distinguishing the metastatic lesions from the benign spinal degenerative changes in the cases with suspicions bone involvement and in evaluating equivocal lesions in the pelvis. Therefore, it was shown that, in the detection and diagnosis of bone metastasis from prostatic cancer, bone scintigraphy alone was insufficient, and that combination with bone marrow scintigraphy was found to be useful. (author)

  19. Bone marrow infection with mycobacterium fortuitum in a diabetic patient

    International Nuclear Information System (INIS)

    Satti, L.; Abbasi, S.; Sattar, A.; Ikram, A.; Manzar, M.A.; Khalid, M.M.

    2011-01-01

    Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin. (author)

  20. Bone marrow NMR imaging and scintigraphy in AIDS patients

    International Nuclear Information System (INIS)

    Theisen, P.; Waters, W.; Schicha, H.; Rasokat, H.; Steigleder, G.K.

    1988-01-01

    The examinations were carried out in order to ascertain whether bone marrow abnormalities can be detected in AIDS patients by means of magnetic resonance imaging or scintiscanning. In 16 of the 19 patients the NMR image and/or the scintiscan distinctly revealed bone marrow abnormalities, but there was no exact correlation to be found to immunological parameters, the peripheral blood picture, or the clinical stage of the HIV infection. (orig.) [de

  1. Whole-body MR imaging of bone marrow

    International Nuclear Information System (INIS)

    Schmidt, G.P.; Schoenberg, S.O.; Reiser, M.F.; Baur-Melnyk, A.

    2005-01-01

    In clinical routine, multimodality algorithms, including X-ray, computed tomography, scintigraphy and MRI, are used in case of suspected bone marrow malignancy. Skeletal scintigraphy is widely used to asses metastatic disease to the bone, CT is the technique of choice to assess criteria of osseous destruction and bone stability. MRI is the only imaging technique that allows direct visualization of bone marrow and its components with high spatial resolution. The combination of unenhanced T1-weighted-spin echo- and turbo-STIR-sequences have shown to be most useful for the detection of bone marrow abnormalities and are able to discriminate benign from malignant bone marrow changes. Originally, whole-body MRI bone marrow screening was performed in sequential scanning techniques of five body levels with time consuming coil rearrangement and repositioning of the patient. The introduction of a rolling platform mounted on top of a conventional MRI examination table facilitated whole-body MR imaging and, with the use of fast gradient echo, T1-weighted and STIR-imaging techniques, for the first time allowed whole-body imaging within less than one hour. With the development of parallel imaging techniques (PAT) in combination with global matrix coil concepts, acquisition time could be reduced substantially without compromises in spatial resolution, enabling the implementation of more complex and flexible examination protocols. Whole-body MRI represents a new alternative to the stepwise multimodality concept for the detection of metastatic disease, multiple myeloma and lymphoma of the bone with high diagnostic accuracy

  2. Total body irradiation in bone marrow transplantation

    International Nuclear Information System (INIS)

    Gluckman, E.; Devergie, A.; Boiron, M.; Bernard, Jean; Dutreix, A.; Dutreix, J.

    1979-01-01

    Total body irradiation was used in 22 patients as part of their conditioning regimen for bone marrow transplantation. Nine patients with acute leukemia received 1000 cGy TBI in addition with chemotherapy. None of them survived and the main cause of death was interstitial pneumonitis (50%). 4 patients received 1000 cGy with a lung shielding of 500 cGy. Two patients with acute leukemia died of leukemia and sepsis, two patients had aplastic anemia, one is surviving, the other died of severe GVHD and infectious complications. Nine patients with severe aplastic anemia strongly immunized by previous blood transfusions received 800 cGy TBI with a lung shielding of 400 cGy. No rejection was observed and 7 patients (63%) are currently alive. One patient died of interstitial pneumonitis probably related to CMV infection, one of subacute necrotizing hepatitis, two of severe acute GVHD. It is concluded from this study that TBI remains the best immunosuppressive conditioning regimen even in strongly immunized patients. It may be a contributing factor of the incidence and severity of interstitial pneumonitis. A reduction of the dose of the lung to 400-500 cGy seems to decrease the severity of this complication

  3. A Bone Marrow Aspirate and Trephine Simulator.

    Science.gov (United States)

    Yap, Eng Soo; Koh, Pei Lin; Ng, Chin Hin; de Mel, Sanjay; Chee, Yen Lin

    2015-08-01

    Bone marrow aspirate and trephine (BMAT) biopsy is a commonly performed procedure in hematology-oncology practice. Although complications are uncommon, they can cause significant morbidity and mortality. Simulation models are an excellent tool to teach novice doctors basic procedural skills before performing the actual procedure on patients to improve patient safety and well-being. There are no commercial BMAT simulators, and this technical report describes the rationale, technical specifications, and construction of a low-cost, easily constructed, reusable BMAT simulator that reproduced the tactile properties of tissue layers for use as a teaching tool in our resident BMAT simulation course. Preliminary data of learner responses to the simulator were also collected. From April 2013 to November 2013, 32 internal medicine residents underwent the BMAT simulation course. Eighteen (56%) completed the online survey, 11 residents with previous experience doing BMAT and 7 without experience. Despite the difference in operative experience, both experienced and novice residents all agreed or strongly agreed that the model aided their understanding of the BMAT procedure. All agreed or strongly agreed that this enhanced their knowledge of anatomy and 16 residents (89%) agreed or strongly agreed that this model was a realistic simulator. We present a novel, low-cost, easily constructed, realistic BMAT simulator for training novice doctors to perform BMAT.

  4. The separation of a mixture of bone marrow stem cells from tumor cells: an essential step for autologous bone marrow transplantation

    International Nuclear Information System (INIS)

    Rubin, P.; Wheeler, K.T.; Keng, P.C.; Gregory, P.K.; Croizat, H.

    1981-01-01

    KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10 6 bone marrow cells. Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored

  5. Study of /sup 201/Tl uptake by bone and bone marrow on /sup 201/Tl scintigraphy. With special reference to bone marrow abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige; Tanaka, Masao; Hirose, Yoshiki; Hirayama, Jiro; Handa, Kenjiro; Nakanishi, Fumiko; Yano, Kesato; Ueda, Hitoshi

    1989-04-01

    Thallium-201 (Tl-201) uptake in the bone and bone marrow was examined in a total of 93 patients with various diseases. Sternal uptake of Tl-201 was observed when patients had bone marrow abnormality especially associated with hematopoietic disease. It was associated with proliferation of immature cells and of various types of bone marrow cells, especially erythroblastic and plasma cells. Whole-body Tl-201 scanning showed a high uptake (82%) in the sternum, chest, lumbar vertebrae, and pelvis. Thallium-201 was definitively taken up by the sternum in polycythemia (5/41), hemolytic anemia (2/2), iron deficiency anemia (2/2), and multiple myeloma (2/5). For leukemia, Tl-201 uptake was slight or negative. Thallium-201 scanning proved useful in visualizing bone marrow abnormality, although careful interpretation of bone and bone marrow uptake is required. (Namekawa, K).

  6. Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

    International Nuclear Information System (INIS)

    Porter, P.N.; Ogawa, M.

    1982-01-01

    Bone marrow conditioned media (BMCM) increases burst number and the incorporation of 59 Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst-promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose-dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture

  7. Bone Marrow Scans with Colloidal {sup 198}Au

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sung Soo; Whang, Kee Suk [Kyungpook National University College of Medicine, Daegu (Korea, Republic of)

    1973-03-15

    The bone marrow scans with colloidal {sup 198}Au were performed on 33 cases with hematologically normal patients and patients with various blood dyscrasia. Bone marrow aspirations were done at iliac crest in all cases but one. A correlation between the scan findings and an erythroid cellularity was evaluated. The following results were obtained. 1) Out of 33 cases, 23 (about 70%) showed a correlation between {sup 198}Au marrow uptakes on the scans and the erythroid cellularity. 2) The diseases in which no correlation existed between {sup 198}Au uptake and erythroid cellularity were aplastic anemia, acute leukemia and chronic myelogenous leukemia.

  8. The production of IL-1, IL-3, CSA by bone marrow nuclears during bone marrow haemopoiesis after lethal irradiation and syngenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Dygaj, A.M.; Buznik, D.V.; Bogdashin, I.V.; Agafonov, V.I.

    1994-01-01

    The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and unadherent cells of lethally irradiate CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoetic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by unadherent bone marrow elements was realised in a late of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells

  9. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  10. Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

    International Nuclear Information System (INIS)

    Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V.

    1990-01-01

    Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases

  11. Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

    Science.gov (United States)

    Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; Cunha, Sandro Torrentes da; Paula, Luis Felipe; Carvalho, Alysson Roncally; Carvalho, Antonio Carlos Campos de; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos

    2017-08-01

    Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

  12. Immune Humanization of Immunodeficient Mice Using Diagnostic Bone Marrow Aspirates from Carcinoma Patients

    Science.gov (United States)

    Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich

    2014-01-01

    Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses. PMID:24830425

  13. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Melanie Werner-Klein

    Full Text Available Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null (NSG and HLA-I expressing NSG mice (NSG-HLA-A2/HHD comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  14. Bone and bone marrow - nuclear medicine in the diagnosis of disorders of the hematopoetic system

    International Nuclear Information System (INIS)

    Cremerius, U.

    1997-01-01

    Significant progress has been achieved during the last years regarding therapy of neoplastic and non-neoplastic diseases of the hematopoietic system by introduction of new therapeutic modalities like highdose chemotherapy, bone marrow and stem cell transplantation, interferon-therapy and others. Diagnosis is still based on biopsy and histopathology of bone marrow. Imaging methods, however, provided by radiology and nuclear medicine, are now increasingly employed to give an additional macroscopic view over morphological and functional changes of the entire bone marrow. Bone marrow scintigraphy either using radiocolloids or immunoscintigraphy against granulocyte-antigenes may be performed as an alternative or an addition to nuclear magnetic resonance imaging. Bone scintigraphy has been successful in the detection of additional bony lesions for more than two decades. Positron emission tomography using 18-fluorine-deoxyglucose has recently been employed as a new and promising tool also for assessment of bone marrow infiltration in malignant lymphomas. (orig.) [de

  15. Bone marrow scintigraphy vs bone scintigraphy and radiography in multiple myeloma

    International Nuclear Information System (INIS)

    Feggi, M.; Prandini, N.; Orzincolo, C.; Bagni, B.; Scutellari, P.N.; Spanedda, R.; Gennari, M.; Scapoli, C.L.

    1988-01-01

    The radiography patterns of the skeleton of 73 patients affected by multiple myeloma (MM) were compared to the correspondent scintigraphic findings. Whole body scans were performed using Tc-diphosphonates 99m (bone scintigraphy). And Tc-microcolloides 99m (bone marrow scintigraphy). The results indicate that: a) radiography is more sensitive and accurate than scintigraphy in detecting typical myeloma-related bone lesions; b) bone scintigraphy is useful in detecting alterations in particular locations-i.e. sternum, ribs, scapulae, etc.-which are difficult to demonstrate by plain X-rays; moreover, the recovery of the fractures can be visualized; c) bone marrow scintigraphy is employed to demonstrate the presence of marrow expasion, of cold/hot spots, and relative marrow uptake, related to phagocytic activity. Since in adult men red marrow is confined to the epiphysis of long bones and to the spine, all the diseases affecting bone marrow cause medullary expansion/reduction, which are both easily detected by specific radiopharmaceuticals. The peripheral expasions is clearly documented especially in distal humeri and femora since marrow uptake is included, in healthy adults, in the axial and proximal appendicular skeleton. In spite of its yielding unique informetion, bone marrow scintigraphy remains an additional technique of bone scan, because of its low diagnoditc accuracy

  16. Radioprotective action on bone marrow CFU during immobilization of mice

    International Nuclear Information System (INIS)

    Keizer, H.J.; van Putten, L.M.

    1976-01-01

    Anesthesia and restraint without anesthesia during whole-body x-irradiation decrease the mortality from both the bone marrow and the intestinal syndromes (30- and 5-day mortality). The two types of immobilization decrease the radiosensitivity of the hemopoietic stem cells, as shown by an increased survival of hemopoietic stem cells in the marrow of immobilized mice. The hypoxic cell radiosensitizer Ro-07-0582 reversed the radioprotective effect during restraint without anesthesia, but not during pentobarbital anesthesia. This indicates that hypoxia of the femur bone marrow cannot explain the decreased radiosensitivity of the stem cells during pentobarbital anesthesia. Pentobarbital was also shown to inhibit the recruitment of resting femur bone marrow stem cells (G 0 -phase cells) into cycle following a sublethal dose of x rays. The relevance of these observations is discussed

  17. T1 value of hyperplastic and hypoplastic bone marrow

    International Nuclear Information System (INIS)

    Asai, Sae; Yoshida, Hideo; Yoshikawa, Hiroki; Yashiro, Naofumi; Iio, Masahiro; Takaku, Fumimaro

    1985-01-01

    Magnetic resonance (MR) images of the bone marrow of 18 patients (11 normal control, 4 aplastic anemia, 2 chronic myelocytic leukemia, 1 polycythemia vera) were discussed. MR imager had 0.15T registive system. Sagittal section of the body was obtained with inversion recovery (TR1,000, 1,600/TI 350, 450/TE 13, 40 msec) and saturation recovery (TR 1,000, 2,000/TE 13,40 msec) sequences. T 1 relaxation time was calculated from those images. T 1 value of the thoracic and lumbar vertebral bone marrow which contains red marrow even in elderly patients was measured. The results were as follows: 1) T 1 values of chronic myelocytic leukemia (CML) and polycythemia vera were longer than that of normal. 2) T 1 values of four aplastic anemia were all shorter than normal. CML and polycythemia vera can be called myeloproliferative disease and their bone marrows are hyperplastic, which may explain elongated T 1 . The bone marrow of aplasticanemia is hypoplastic and shows fatty change which may have decreased T 1 . Our results suggest T 1 value of bone marrow is useful to evaluate hematological disorders. (author)

  18. Developmental and radiobiologic characteristics of canine multinucleated, osteoclast-like cells generated in vitro from canine bone marrow

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.; Domann, F.; Niiro, G.K.; LeBuis, D.A.

    1988-01-01

    We report here our initial observations on the growth and morphology, and developmental radiosensitivity of giant, multinucleated, osteoclast-like cells (MN-OS) generated through in vitro cultivation of hematopoietic progenitor-enriched canine bone marrow samples. Maximum cell densities of 5.5 x 10(3) to 6.5 x 10(3) MN-OS per cm2 of growth area were achieved following 10 to 14 days of culture at 37 degrees C. Acute gamma irradiation of the initial marrow inocula resulted in significant, dose-dependent perturbations of MN-OS formation, growth, and development. Attempts to estimate radiosensitivity of MN-OS progenitors from canine marrow yielded a range of Do values from a low of 212 cGy measured at six days of culture to higher values of 405 to 542 cGy following 10 to 22 days of culture. At the intermediate times of culture (10 to 14 days), the radiation-induced responses were clearly biphasic, reflecting either (a) the presence of multiple subpopulations of MN-OS progenitors with varying degrees of radiosensitivity or (b) the inherent biphasic nature of MN-OS development involving early progenitor cell proliferation followed by maturation and subsequent fusion. Morphologically, MN-OS generated from irradiated marrow inocula appeared only marginally altered, with alterations expressed largely in a biphasic, dose-dependent fashion in terms of smaller cell size, reduced number of nuclei, increased expression of both surface microprojections, and a unique set of crystalloid cytoplasmic inclusions. Functionally, MN-OS appeared to be impaired by irradiation of marrow progenitors, as evidenced by failure to initiate resorptive attachments to devitalized bone spicules in vitro

  19. Bone and bone marrow function of reconstructed chest wall after surgical correction of pectus excavatum

    International Nuclear Information System (INIS)

    Watanabe, Yoh; Magara, Tatsuo; Kobayashi, Hiroaki; Ichihashi, Takumi; Hikishima, Hiroshi

    1984-01-01

    Bone and Bone marrow functions of the reconstructed chest wall after surgical correction of the funnel chest deformities were evaluated by scanning method. In our series, three kinds of operative procedures were employed; strut method for adult cases, sternal turnover method with and without muscle pedicle for infant cases. Bone function was scanned by sup(99m)Tc-methylene-diphosphonate and bone marrow function was evaluated by sup(99m)Tc-sulfur-colloid. For the cases undergone each surgical procedure, bone and bone marrow scan were done at short term after surgery (within 30 days), at intermediate stage (one month to 12 months), and at long term stage (beyond one year). The results were as follows: By the evaluation at the long term stage of the cases undergoing strut method, bone as well as bone marrow scan visualized normal view of the reconstructed sternum. Regarding the cases undergone sternal turnover method without muscle pedicle, or free graft implantation of the plastron, the bone scan at the long term follow-up stage showed abnormal finding, i.e. hypo-, or defect-visualization of the inverted sternum, in 11.5% of the cases. Furthermore, bone marrow scan showed abnormality in 33.3% of the cases. On the other hand, the cases undergone sternal turnover method with muscle pedicle, in which blood supply to the plastron were preserved by the connection from superior epigastric artery to internal mammary artery, showed no abnormality as far as at the long term follow-up study neither in bone scan nor bone marrow scan. However, in the evaluation at short term after surgery, 50% of the cases undergoing bone scan showed abnormality. In addition, in this stage 85.7% of the bone marrow scan showed abnormal finding. These abnormality, however, normalized within 6 months for bone scan and 12 months for bone marrow scan, in contrast to the results of the cases undergone sternal turnover without pedicle. (J.P.N.)

  20. ROLE OF BONE MARROW ASPIRATION IN DIAGNOSIS OF HAEMATOLOGICAL DISORDER

    Directory of Open Access Journals (Sweden)

    Poonam Nanwani

    2017-03-01

    Full Text Available BACKGROUND The bone marrow examination is an essential investigation for the diagnosis of disorders of the blood and bone marrow. This simple and relatively safe procedure is important, particularly in resource poor centres since access to adjuvant diagnostic techniques are often lacking or absent. MATERIALS AND METHODS 189 patients of all age groups were studied for haematological and non-haematological disorders by bone marrow aspiration in the Department of Pathology, MGM Medical College during the period of 2014 to 2016. RESULTS Majority of the patients who had bone marrow aspiration were aged 0-15 years. The male-to-female ratio was 1:1.03. Most (97% of the marrow aspirate examined had definitive pathologic features, while 14 (7% were normal marrow elements. Out of 189 cases of bone marrow aspiration, acute leukaemia was the most common haematological disease diagnosed using this procedure. Acute lymphoblastic leukaemia was more common than acute myeloid leukaemia. Aplastic anaemia was seen in 16% cases. Megaloblastic anaemia occurred more commonly than other anaemias. Megaloblastic anaemia was seen in 13 cases (7% and microcytic anaemia was seen in 5 cases (3%. There were 10 cases (5% of Idiopathic Thrombocypenic Purpura. Myelodysplastic syndrome and multiple myeloma was seen in 7% and 2% cases respectively. Storage disorder was seen in 3 cases (2%, out of this 02 cases were Gaucher’s disease and one case was Niemann-Pick’s disease. CONCLUSION Bone marrow examination is an important step to arrive at the confirmatory diagnosis of many haematological disorders. This procedure remains a veritable tool in the diagnosis and management of a wide range of haematological diseases, especially in a resource poor centre.

  1. Proliferative activity of vervet monkey bone marrow-derived adherent cells

    International Nuclear Information System (INIS)

    Kramvis, A.; Garnett, H.M.

    1987-01-01

    Vervet monkey bone marrow-derived adherent cell population cultured in Fischer's medium supplemented with 12.5% fetal calf serum and 12.5% horse serum consists of two cell shapes: fusiform (type I) and polygonal (type II). Limiting-dilution cloning of the cells suggested that the two morphologically distinct cell types belong to the same cellular system even though they differ in their proliferative capabilities. The labeling index of type II cells, as measured by autoradiography, was found to be consistently lower than that of type I cells. It is probable that these two phenotypes represent different stages of differentiation, where progenitor type I gives rise to type II cells. The bone marrow-derived adherent cells were found to be cytokinetically at rest in vivo, using the thymidine suicide test, and relatively radioresistant with a D0 = 2.1 Gy and n = 2.36 at the time of explantation from the bone. Furthermore, in culture these cells are characterized by a relatively long cell cycle of 60 h, where the length of the S phase is 30 h, G2 is 12 h, M is 6 h, and G1 is 12 h. Thus, the vervet monkey bone marrow-derived adherent cells represent a cell population with a low turnover rate both in vivo and in vitro

  2. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

    Science.gov (United States)

    Tormin, Ariane; Li, Ou; Brune, Jan Claas; Walsh, Stuart; Schütz, Birgit; Ehinger, Mats; Ditzel, Nicholas; Kassem, Moustapha

    2011-01-01

    Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin−/CD271+/CD45−/CD146+ stem-cell fraction, but also in lin−/CD271+/CD45−/CD146−/low cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34+ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment. PMID:21415267

  3. Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage

    International Nuclear Information System (INIS)

    Thiryayi, W.A.; Thiryayi, S.A.; Freemont, A.J.

    2008-01-01

    This article presents a systematic review of the current biomedical literature surrounding the aetiopathogenesis and histopathological features of bone marrow oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally demonstrated as a non-specific finding on magnetic resonance imaging in association with infections, tumours and avascular necrosis. When it occurs in isolation as a primary event not triggered by any obvious bony pathology in the clinical setting of debilitating joint pain, it constitutes the 'bone marrow oedema syndrome'. Although the latter diagnosis is based on magnetic resonance (MR) imaging, showing the lesion as areas of signal hyperintensity within the marrow, recent radiology-histology correlational studies have shown variably interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities. In light of these facts, the use of the term bone marrow oedema syndrome in a radiological context might be considered questionable, but histopathological techniques are not sensitive in detecting increased extracellular fluid. Reactive bone changes may be focal or diffuse and usually amount to increased bone formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a condition in which the size of the bruise and associated osteochondral injury determines the outcome, although the natural history of these lesions is still being researched

  4. Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Thiryayi, W.A.; Thiryayi, S.A. [Department of Histopathology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL (United Kingdom); Freemont, A.J. [Division of Regenerative Medicine, University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom)], E-mail: tony.freemont@manchester.ac.uk

    2008-07-15

    This article presents a systematic review of the current biomedical literature surrounding the aetiopathogenesis and histopathological features of bone marrow oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally demonstrated as a non-specific finding on magnetic resonance imaging in association with infections, tumours and avascular necrosis. When it occurs in isolation as a primary event not triggered by any obvious bony pathology in the clinical setting of debilitating joint pain, it constitutes the 'bone marrow oedema syndrome'. Although the latter diagnosis is based on magnetic resonance (MR) imaging, showing the lesion as areas of signal hyperintensity within the marrow, recent radiology-histology correlational studies have shown variably interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities. In light of these facts, the use of the term bone marrow oedema syndrome in a radiological context might be considered questionable, but histopathological techniques are not sensitive in detecting increased extracellular fluid. Reactive bone changes may be focal or diffuse and usually amount to increased bone formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a condition in which the size of the bruise and associated osteochondral injury determines the outcome, although the natural history of these lesions is still being researched.

  5. Scintigraphy of bone marrow for neoplastic lesions in breast carcinoma

    International Nuclear Information System (INIS)

    Takacs, J.; Zimacek, J.; Wagnerova, M.; Szabova, J.; Sirakova, I.; Frolo, D.

    1989-01-01

    Bone marrow scintigraphy was performed in 259 patients including 124 females with breast carcinoma using the technique of 99m Tc-labelled colloid retention by phagocytizing cells, thus visualizing the reticuloendothelial component of the bone marrow. The objective was to early diagnose hematogenic metastases. In five patients, simultaneous skeleton scintiscanning was not performed. The technique was shown to play a role in early diagnosis of bone metastases and of bone lesions in less usual loci and especially in the differential diagnosis of nonmalignant bone disease, such as arthrosis. Its constraints include an intensive cumulation of the radiopharmaceutical in the liver and the splenic reticuloendothelial systems, which precludes the assessment of the bone marrow in the adjacent areas; further a difficult interpretation of the results, high cost and long time of examination. It has no role in patients with disseminated forms of the disease with multiple bone metastases already shown by scintigraphy. Bone marrow scintigraphy alone is not a reliable method for early diagnosis of breast carcinoma (L.O.)

  6. Is fatty acid composition of human bone marrow significant to bone health?

    Science.gov (United States)

    Pino, Ana María; Rodríguez, J Pablo

    2017-12-16

    The bone marrow adipose tissue (BMAT) is a conserved component of the marrow microenvironment, providing storage and release of energy and stabilizing the marrow extent. Also, it is recognized both the amount and quality of BMAT are relevant to preserve the functional relationships between BMAT, bone, and blood cell production. In this article we ponder the information supporting the tenet that the quality of BMAT is relevant to bone health. In the human adult the distribution of BMAT is heterogeneous over the entire skeleton, and both BMAT accumulation and bone loss come about with aging in healthy populations. But some pathological conditions which increase BMAT formation lead to bone impairment and fragility. Analysis in vivo of the relative content of saturated and unsaturated fatty acids (FA) in BMAT indicates site-related bone marrow fat composition and an association between increased unsaturation index (UI) and bone health. With aging some impairment ensues in the regulation of bone marrow cells and systemic signals leading to local chronic inflammation. Most of the bone loss diseases which evolve altered BMAT composition have as common factors aging and/or chronic inflammation. Both saturated and unsaturated FAs originate lipid species which are active mediators in the inflammation process. Increased free saturated FAs may lead to lipotoxicity of bone marrow cells. The pro-inflammatory, anti-inflammatory or resolving actions of compounds derived from long chain poly unsaturated FAs (PUFA) on bone cells is varied, and depending on the metabolism of the parent n:3 or n:6 PUFAs series. Taking together the evidence substantiate that marrow adipocyte function is fundamental for an efficient link between systemic and marrow fatty acids to accomplish specific energy or regulatory needs of skeletal and marrow cells. Further, they reveal marrow requirements of PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effects of Spaceflight on Cells of Bone Marrow Origin

    Directory of Open Access Journals (Sweden)

    Engin Özçivici

    2013-03-01

    Full Text Available Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types.

  8. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

  9. Context Matters: Distinct Disease Outcomes as a Result of Crebbp Hemizygosity in Different Mouse Bone Marrow Compartments.

    Directory of Open Access Journals (Sweden)

    Ting Zhou

    Full Text Available Perturbations in CREB binding protein (CREBBP are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS. Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U, and a proportion goes on to develop acute myeloid leukemia (AML. We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells. We now report that transplantation of unfractionated Crebbp+/- bone marrow into wild-type recipients resulted in either early-onset AML or late-onset MDS and MDS/MPN-U. In contrast, purified Lin-Sca-1+c-Kit++ cells primarily gave rise to MDS with occasional transformation to AML. Furthermore, Crebbp+/- common myeloid progenitors and granulocyte/macrophage progenitors could trigger skewed myelopoiesis, myelodysplasia and late-onset AML. Surprisingly, the phenotypically abnormal cells were all of wild-type origin. MDS, MPN and AML can thus all be transferred from Crebbp+/- BM to wild-type hosts but fractionated bone marrow does not recapitulate the full disease spectrum of whole bone marrow, indicating that not only mutational status but also cellular context contribute to disease outcome. This has important consequences for structuring and interpreting future investigations into the underlying mechanisms of myeloid malignancies as well as for their treatment.

  10. High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice

    DEFF Research Database (Denmark)

    Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas

    2018-01-01

    that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison...... to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory...... demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin...

  11. Posttherapeutic changes in bone marrow; Posttherapeutische Veraenderungen am Knochenmark

    Energy Technology Data Exchange (ETDEWEB)

    Geith, T.; Stellwag, A.C.; Baur-Melnyk, A. [Klinikum der Universitaet Muenchen, Klinik und Poliklinik fuer Radiologie, Muenchen (Germany)

    2017-11-15

    The bone marrow basically consists of red blood-forming bone marrow and yellow fat. In the skeleton, there is an age-dependent distribution of these two parts. In the context of medical interventions or therapies, bone marrow changes can occur, whereby the normal bone marrow can basically be replaced by fat, edema, or fibrosis/sclerosis. Here, specific signal intensities and patterns are shown in imaging. After irradiation therapies, edematous changes, hemorrhages, and osteoradionecroses are observed. Likewise, insufficiency fractures, impairment of the growth gaps, or the development of tumors is possible. In patients on dialysis, deposit of protein in the bone marrow is possible in the case of the so-called amyloidosis osteoarthropathy. Postoperative bone marrow edema, insufficiency fractures, or osteonecrosis can be observed after arthroscopy. Changes in the distribution of fat markers and blood-forming bone marrow can be observed after stem cell transplants. In the therapy with cortisone, insufficiency fractures and osteonecroses are possible. Depending on their effect on the hematopoietic system, chemotherapies can first lead to edematous changes and then to fatty bone marrow, which is reversible after therapy. Angiogenesis inhibitors in combination with other chemotherapeutic agents often lead to mixed images of stimulated and fatty bone marrow. (orig.) [German] Das Knochenmark besteht grundsaetzlich aus rotem blutbildenden Knochenmark und gelbem Fettmark. Im Skelett besteht eine altersabhaengige Verteilung dieser beiden Anteile. Im Rahmen von aerztlichen Eingriffen oder Therapien kann es zu Veraenderungen des Knochenmarks kommen, wobei das normale Knochenmark grundsaetzlich durch Fett, Oedem oder Fibrose/Sklerose ersetzt werden kann. Dabei zeigen sich in bildgebenden Verfahren spezifische Signalintensitaeten und Muster. Nach Bestrahlungstherapien sind oedematoese Veraenderungen, Haemorrhagien und Osteoradionekrosen zu beobachten. Ebenso sind

  12. Evaluation of bone marrow in patients with pancytopenia

    Directory of Open Access Journals (Sweden)

    R Pathak

    2012-09-01

    Full Text Available Background: Pancytopenia is a common hematological finding resulting from varieties of disease processes that require evaluation of bone marrow. This study was carried out to evaluate bone marrow findings in patients presenting with pancytopenia.Materials and Method: This was a prospective cross sectional study carried out to identify the causes of pancytopenia based on bone marrow examination. Bone marrow examinations were performed in 503 cases for different indications over a period of one year.Results: One hundred and two (20.27% cases fulfilled the criteria of pancytopenia. Trephine biopsy was possible only in 48 cases. In 75% cases aspiration findings were similar to biopsy. Mean age of patients was 38.8 years. Maximum number of cases was seen in age group of 15-30 years. Hypoplastic anemia was the commonest cause followed by hematological malignancies, megaloblastic anemia, leishmaniasis and Gaucher disease. Bone marrow examination alone was able to establish the diagnosis in 76.5% cases. In rest marrow findings were nonspecific and in 4.9% cases findings were normal.Conclusion: Bone marrow aspiration coupled with trephine biopsy can diagnose majority but not all the cases of pancytopenia. Hypoplastic anemia, hematological malignancies and megaloblastic anemia are the commonest causes of pancytopenia. Maximum diagnostic yield can be achieved by correlation with clinical findings, peripheral blood findings and with other laboratory and radiological parameters.Journal of Pathology of Nepal (2012 Vol. 2, 265-271DOI: http://dx.doi.org/10.3126/jpn.v2i4.6875

  13. Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells

    DEFF Research Database (Denmark)

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad

    2016-01-01

    and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular......Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional...... and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures...

  14. Late taste disorders in bone marrow transplantation: clinical evaluation with taste solutions in autologous and allogeneic bone marrow recipients.

    Science.gov (United States)

    Marinone, M G; Rizzoni, D; Ferremi, P; Rossi, G; Izzi, T; Brusotti, C

    1991-01-01

    The aim of this work was to determine the type and the significance of taste disorders in allogeneic bone marrow transplanted patients. In a retrospective study the taste threshold of a cohort of 15 allogeneic bone marrow transplanted patients, 4-51 months after transplantation (mean: 30.6 +/- 15.8), was compared to the taste threshold of 8 autologous bone marrow recipients, 4-48 months after transplantation (mean: 24.12 +/- 12.18), and to the taste threshold of a group of 20 consecutive normal subjects. Allogeneic bone marrow transplanted patients showed a significant hypogeusia for salt (Pearson's chi square p = 0.0002; Yates' correction p = 0.0007) and sour (Pearson's chi square p = 0.001; Yates' correction p = 0.008). No significant variations were observed for sweet and bitter. Autologous bone marrow recipients did not show any significant variation of taste acuity for sweet, salt or sour; a constant reduction of the taste threshold for bitter was observed, but the values were not significantly different from normal (Pearson's chi square p = 0.47; Yates' correction p = 0.83). So, late and selective taste disorders are observed in allogeneic bone marrow transplanted patients. Since the severity of the disorders is not strictly related to the severity of chronic oral G.V.H.D., taste analysis could discover the slightest, clinically undetectable cases of chronic oral G.V.H.D. The mechanism of immune aggression on the sensorial taste cells is poorly understood. Further trials are needed to define variations of taste acuity not only after allogeneic bone marrow transplantation, but also in systemic immune diseases.

  15. [MRI characteristic of proximal femur bone marrow edema syndrome].

    Science.gov (United States)

    Wu, Xi-Yuan

    2014-07-01

    To study the MRI features of proximal femur bone marrow edema syndrome for further improve the understanding of the disease. MRI imaging of 10 patients with proximal femur bone marrow edema syndrome was retrospectively reviewed,including 6 males and 4 females with an average age of 41.5 years old ranging from 36 to 57. The courses of diseases ranged from 1 week to 3 months. Among them, 9 cases had clinical manifestations of sudden hip pain, 7 cases had limited ability of walking and hip movement;all patients had no obvious injury history, non of the female patients was pregnant. All patients were followed up from 3 to 12 months, the following-up were topped after MRI when the symptoms disappeared for 3 months. The MRI demonstrated diffuse bone marrow edema involving the femoral head, neck and the inter-trochanteric region, 13 hips of 10 patients with bone marrow edema included 6 cases in grade 1, 5 cases in grade 2,2 cases in grade 3; 9 hips with hip hydrarthrosis included 6 hips in grade I ,1 hip in grade II, 2 hips in grade III. After treatment for 3 to 12 months the hip symptoms of the patients disappeared and MRI images were normal. MRI is useful in defining the location and extent of proximal femur bone marrow edema syndrome.

  16. Lasting engraftment of histoincompatible bone marrow cells in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  17. Lasting engraftment of histoincompatible bone marrow cells in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  18. Lasting engraftment of histoincompatible bone marrow cells in dogs

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-01-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed

  19. Cells derived from young bone marrow alleviate renal aging.

    Science.gov (United States)

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  20. Bone marrow-derived T lymphocytes responsible for allograft rejection

    International Nuclear Information System (INIS)

    Senjanovic, M.; Marusic, M.

    1984-01-01

    Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

  1. Bone marrow examination in itp in children is it mandatory

    International Nuclear Information System (INIS)

    Ahmad, Z.; Durrani, N.U.R.; Hazir, T.

    2007-01-01

    To determine the need of bone marrow examination in children with idiopathic thrombocytopenic purpura (ITP) at initial presentation. All children, clinically suspected to have ITP, who underwent bone marrow examination, were included After reviewing the file records of these patients for history, examination and investigations, a predesigned proforma was filled and data was analyzed, using SPSS version 10 for statistical analysis. The results were reported in the form of frequencies, percentages and mean. A majority of the children were between 48 to 96 months, with a mean age of 54.43 months. Male to female ratio was 1.45:1. Mean platelet count was 33861/mm3. None of the bone marrow results showed the presence of abnormal cells consistent with hematological malignancy. ITP was the final diagnosis in 52 patients. One patient was diagnosed to have megakaryocytic hypoplasia. Bone marrow aspiration in one patient was hypoplastic, and subsequently, he was diagnosed to have aplastic anemia on trephine biopsy. Bone marrow aspiration should not be a part of routine work-up for diagnosing ITP in children and should be reserved for those children having atypical clinical and laboratory features. (author)

  2. What Is a Bone Marrow Transplant?

    Science.gov (United States)

    ... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... Copyright © 1996-2018 National Marrow Donor Program. All Rights Reserved.

  3. Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen.

    Science.gov (United States)

    Capitano, Maegan L; Chitteti, Brahmananda R; Cooper, Scott; Srour, Edward F; Bartke, Andrzej; Broxmeyer, Hal E

    2015-06-01

    Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice. Copyright © 2015. Published by Elsevier Inc.

  4. PET/CT versus bone marrow biopsy in the initial evaluation of bone marrow infiltration in various pediatric malignancies.

    Science.gov (United States)

    Zapata, Claudia P; Cuglievan, Branko; Zapata, Catalina M; Olavarrieta, Raquel; Raskin, Scott; Desai, Kavita; De Angulo, Guillermo

    2018-02-01

    Accurate staging is essential in the prognosis and management of pediatric malignancies. Current protocols require screening for marrow infiltration with bone marrow biopsy (BMB) as the gold standard. Positron emission tomography-computed tomography (PET-CT) is commonly used to complete the staging process and can also be used to evaluate marrow infiltration. To compare PET-CT and BMB in the initial evaluation of bone marrow infiltration in pediatric cancers. We retrospectively reviewed new cases of EWS, rhabdomyosarcoma, neuroblastoma, and lymphoma diagnosed between January 2009 and October 2014. Each case had undergone both PET-CT and BMB within 4 weeks without treatment in the interval between screening modalities. We reviewed 69 cases. Bone marrow infiltration was demonstrated in 34 cases by PET-CT and in 18 cases by BMB. The sensitivity and negative predictive value of PET-CT were both 100%. Interestingly, the cases in which infiltration was not detected on BMB had an abnormal marrow signal on PET-CT focal or distant to iliac crest. PET-CT has a high sensitivity when assessing marrow infiltration in pediatric malignancies. Advances in radiologic modalities may obviate the use of invasive, painful, and costly procedures like BMB. Furthermore, biopsy results are limited by insufficient tissue or the degree of marrow infiltration (diffuse vs. focal disease). PET-CT can improve the precision of biopsy when used as a guiding tool. This study proposes the use of PET-CT as first-line screening for bone marrow infiltration to improve the accuracy of staging in new diagnoses. © 2017 Wiley Periodicals, Inc.

  5. A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

    Science.gov (United States)

    Tamary, H; Yaniv, I; Stein, J; Dgany, O; Shalev, Z; Shechter, T; Resnitzky, P; Shaft, D; Zoldan, M; Kornreich, L; Levy, R; Cohen, A; Moser, R A; Kapelushnik, J; Shalev, H

    2003-09-01

    Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

  6. Bone marrow transplantation for an infant with neutrophil dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Camitta, B M; Quesenberry, P J; Parkman, R; Boxer, L A; Stossel, T P; Cassady, J R; Rappeport, J M; Nathan, D G [Harvard Medical School, Boston, Mass. (USA); Tufts Univ., Boston, Mass. (USA). School of Medicine)

    1977-01-01

    A child with severe neutrophil dysfunction and intractable infections received bone marrow transplants from histocompatible siblings. After a first transplant preceded by cyclophosphamide (CY), antithymocyte serum (ATS) and procarbazine (PCB) preconditioning, there was no evidence for engraftment and autologous marrow function rapidly returned. Cell mediated lysis showed no evidence of patient sensitization against the marrow donor suggesting that graft rejection did not cause the transplant failure. A second transplant was performed utilizing another matched sibling donor. Total body irradiation was added to CY, ATS, and PCB for preconditioning after in vitro studies of the colony forming capacity (CFUsub(c)) of the patient's marrow cells showed normal sensitivity to radiation. Full engraftment ensued with correction of granulocyte function abnormalities. The patient eventually died of intractable pulmonary disease. Experience with this child suggests that cyclophosphamide alone may be insufficient preparation for marrow transplantation in some patients with non-neoplastic hematologic disorders. Experimental and clinical data supporting this contention are reviewed.

  7. Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.

    Science.gov (United States)

    Chang, C H; Stanton, R P; Glutting, J

    2002-04-01

    In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts.

  8. Effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition

    International Nuclear Information System (INIS)

    Gao Yong; Zhang Weiguang

    2004-01-01

    Objective: To provide scientific information for the prevention and treatment of the radiation damage by analyzing the effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition. Methods: 7 group mice were exposed to smoke and/or tea and/or radiation respectively. There were also b blank control group and a cyclophosphamide positive control group. The frequencies of micronucleated polychromatic erythrocytes (MPCE), the ratio of polychromatic erythrocytes (PCE) to mature erythrocytes (RBC) in marrow, and the count of peripheral blood hemoleukocyte were observed. Results: The frequencies of MPCE in the groups irradiated with γ-rays were significantly higher than that in the blank control group (P<0.05 or 0.01). The smoke + radiation group's frequency was significantly higher than single radiation group (P<0.05). The ratios of PCE to RBC in the groups irradiated were significantly lower than that in the blank control group (P<0.01). The counts of peripheral blood hemoleukocyte in the groups irradiated were significantly lower than the blank control group (P<0.01). Conclusion: Radiation were able to cause marrow cell mutation and induce marrow inhibition. Smoke increases the effect of radiation-induced marrow cell mutation. Tea and smoke could not affect radiation-induced bone marrow inhibition

  9. Prognosis and bone marrow recovery indicators in bone marrow transplantation after total body irradiation

    International Nuclear Information System (INIS)

    Dubner, Diana; Perez, Maria del R.; Gisone, Pablo; Barboza, Marcos; Sorrentino, Miguel; Robinson, Anibal

    2002-01-01

    Oxidative stress and reticulocyte maturity index (RMI) were studied in 27 patients who underwent bone marrow transplantation (BMT). Plasmatic lipo peroxide levels of those patients with unfavorable evolution were significantly increases on days 12-14 post-transplant (median 1,83 μM, range 0.78-5.82) compared with preconditioning levels (median 1.05 μM, range 0.36-1.84) (p<0.05). Patients with favorable evolution revealed significantly higher lipo peroxide levels during conditioning regime (median 1.42 μM, range 0.31-4.50) (p<0.05). Starting from the 3rd. post-transplant week a significant and continuous decrease was observed, with a median of 0.77 μM (range 0.21-1.48) (p<0.05) for the 3rd, and a median of 0.60 μM (range 0.11-1.48) for the 4th. week (p<0.01). A significant increase in total antioxidant activity was observed in the three patients who died up to the 35 days post-transplant. Recovery of bone marrow function was detected by RMI after a median time of 17 days (range 11-24) post-allogeneic transplantation. The threshold established for absolute neutrophil count was achieved after a median of 21 days (range 14-28) (p<0.001). An increase of plasma lipo peroxides on days 12-14 post transplant may be a predictive value of unfavourable evolution. RMI was the earlier indicator of engraftment in allogeneic BMT. (author)

  10. Safety assessment of bone marrow derived MSC grown in platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Shoji Fukuda

    2015-06-01

    Full Text Available The injection of endothelial progenitor cells and mononuclear cells derived from bone marrow at the ischemic region of peripheral artery disease patients is reported to be effective for therapeutic angiogenesis; however, these cell therapies require large amounts of bone marrow to obtain sufficient numbers of cells. To solve this problem, we attempted to culture bone-marrow-derived mesenchymal stem cells (BM-MSC, which are supposed to secrete several cytokines that promote angiogenesis. We also focused on using platelet-rich plasma (PRP as a supplement for cell culture instead of fetal bovine serum. Human BM-MSC obtained from healthy volunteers expanded rapidly when cultured with 10% PRP prepared from their own blood. FACS analysis revealed that these cultured human MSC were homogeneous populations, and chromosomal analysis showed a normal karyotype. Moreover, the angiogenetic effect was apparent two weeks after human BM-MSC were injected into the ischemic muscle in SCID mice. Tumor formation was not detected three months after injection into SCID mice either subcutaneously or intramuscularly. To simulate clinical settings, canine BM-MSC were grown with canine PRP and injected into their ischemic muscles. We confirmed that donor cells existed in situ two and six weeks after operation without any side effects. These results suggest that cultured human BM-MSC can be a promising cell source for therapeutic angiogenesis.

  11. Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.

    Science.gov (United States)

    Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio

    2011-01-01

    Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.

  12. Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

    Directory of Open Access Journals (Sweden)

    Clifford J Rosen

    2016-10-01

    Full Text Available The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-­‐invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation.

  13. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Shoichiro Kokabu

    2016-01-01

    Full Text Available Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3, which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment.

  14. Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

    OpenAIRE

    Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

    2015-01-01

    Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (?-TCP, without coating or ...

  15. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  16. Absorbed bone marrow dose in certain dental radiographic techniques

    International Nuclear Information System (INIS)

    White, S.C.; Rose, T.C.

    1979-01-01

    The absorbed dose of radiation in the bone marrow of the region of the head and neck was measured during intraoral, panoramic, and cephalometric radiography. Panoramic radiography results in a dose a fifth or less than that from an intraoral survey. The use of rectangular collimation reduces the bone marrow absorbed dose from an intraoral survey by about 60%. Comparison of the doses from dental radiography with natural environmental radiation shows that an intraoral set of films results in the same total dose to the bone marrow as 65 days of background exposure. The use of rectangular collimation reduces this value to 25 days. Panoramic radiography results in significantly less irradiation, as it reduces the value to 14 days or fewer. Dental radiography thus involves exposures in the range of variation of natural environmental background values

  17. Whole bone marrow irradiation for the treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Coleman, M.; Saletan, S.; Wolf, D.; Nisce, L.; Wasser, J.; McIntyre, O.R.; Tulloh, M.

    1982-01-01

    Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the ''three and two'' total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma

  18. Noradrenergic and cholinergic innervation of the bone marrow.

    Science.gov (United States)

    Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

    2002-07-01

    Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

  19. The recovery of bone marrow derived GM-CFU in baboons unilaterally exposed to a total body LD50/30d mixed neutron-gamma irradiation

    International Nuclear Information System (INIS)

    Herodin, F.; Orfeuvre, H.; Janodet, D.; Mestries, J.C.; Fatome, M.

    1990-01-01

    The unilateral exposure of baboons to a total body LD 50/30d mixed neutron/gamma irradiation was characterized to be non uniform in dose distribution. The pattern of recovery of granulocyte-macrophage progenitors in bone marrow samples collected from entrance and exit sides respectively is consistent with this observed heterogeneity [fr

  20. Relationship of bone marrow dose to eosinophilia following radiotherapy

    International Nuclear Information System (INIS)

    Murohashi, Ikuo; Gomi, Hiromichi; Nakano, Takashi; Morita, Shinroku; Arai, Tatsuo; Jinnai, Itsuro; Nara, Nobuo; Bessho, Masami; Hirashima, Kunitake.

    1986-01-01

    Absolute blood eosinophils were counted prior to and during radiotherapy in a total of 380 patients with carcinoma in the chest, pelvis, or abdomen. The patients were divided into 5 groups by types of cancer, and these groups differed in the irradiation sites or the sizes of radiation field. Accumulated bone marrow dose from the start of radiotherapy to the time when eosinophil count during radiotherapy reached its peak was simultaneously determined. In each group, maximum eosinophil count during radiotherapy was significantly increased compared with the value before radiotherapy. In all groups except one, the increase in eosinophil count following radiotherapy was directly proportional to the bone marrow dose. However, in the most heavily irradiated ovarian cancer group, the increase in eosinophil count was markedly lower. In contrast, neutrophils were reduced in numbers in all groups. These results suggest that bone marrow (red marrow) damage by irradiation results in eosinophilia, and that unimpaired hemopoiesis is also indispensable for such an eosinophil response. Accumulated bone marrow doses of 800 - 900 rad given during 4 weeks fractionated irradiation caused the most prominent eosinophilia. (author)

  1. Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

    Science.gov (United States)

    Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

    2016-01-01

    The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

  2. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

    Directory of Open Access Journals (Sweden)

    Christian Hendrich

    2009-12-01

    Full Text Available The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications For this purpose, the clinical-radiological progress of a total of 101 patients with various bone healing disturbances was documented (surveillance study. The study included 37 necrosis of the head of the femur, 32 avascular necroses/bone marrow edema of other localization, 12 non-unions, 20 other defects. The application of BMAC was performed in the presence of osteonecrosis via a local injection as part of a core decompression (n=72 or by the local adsorption of intra-operative cellular bone substitution material (scaffold incubated with BMAC during osteosynthesis (n=17 or in further surgery (n=12. After an average of 14 months (2-24 months, the patients were re-examined clinically and radiologically and interviewed. Further surgery was necessary in 2 patients within the follow-up period. These were due to a progression of a collapsed head of the femur with initial necrosis in ARCO Stage III, as well as inadequate new bone formation with secondary loss of correction after periprosthetic femoral fracture. The latter healed after repeated osteosynthesis plus BMAC application without any consequences. Other than these 2 patients, no further complications were observed. In particular, no infections, no excessive new bone formation, no induction of

  3. The usefulness of bone-marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Sone, Teruki; Yoneda, Masaya; Tomomitsu, Tatsushi; Yanagimoto, Shinichi; Muranaka, Akira; Morita, Rikushi; Saito, Noriaki; Tanaka, Hiroyoshi

    1985-01-01

    We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose sup(99m)Tc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients, were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by sup(99m)Tc-MDP bone scintigraphy, sup(99m)Tc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis. (orig.)

  4. The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

    Science.gov (United States)

    Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

    2014-01-01

    Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

  5. Bone marrow aspiration and biopsy. Technique and considerations

    Directory of Open Access Journals (Sweden)

    R.A. Trejo-Ayala

    2015-10-01

    Full Text Available Bone marrow aspiration and bone marrow biopsy are invasive procedures in which good technical skill is crucial to obtain samples suitable for processing and diagnostic interpretation. The type and calibre of the needle is one of the main variables of the technique, and is selected on the basis of the age, gender and body mass of the patient. This article provides a practical, step-by-step guide to the technique for both procedures. It also discusses existing techniques for reducing the pain associated with the procedure, an essential aspect for the patient that if poorly handled, can force cancellation of the procedure.

  6. System for estimation of mean active bone marrow dose

    International Nuclear Information System (INIS)

    Ellis, R.E.; Healy, M.J.R.; Shleien, B.; Tucker, T.

    1975-09-01

    The exposure measurements, model and computer program for estimation of mean active bone marrow doses formerly employed in the 1962 British Survey of x-ray doses and proposed for application to x-ray exposure information obtained in the U.S. Public Health Service's X-Ray Exposure Studies (1966 and 1973) are described and evaluated. The method described is feasible for use to determine the mean active bone marrow doses to adults for examinations having a skin to source distance of 80 cm or less. For a greater SSD, as for example in chest x rays, a small correction in the calculation dose can be made

  7. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V

    1978-01-01

    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA......-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had...

  8. Bone marrow transplantation for correction of enzyme deficiency disease

    International Nuclear Information System (INIS)

    Hong, C.; Sutherland, D.E.R.; Matas, A.J.; Najarian, J.S.

    1979-01-01

    Mutant acatalasemic mice provide a prototype of congenital enzyme deficiency disease. Normal blood catalase levels were achieved permanently in congenitally acatalasemic mice by transplantation of bone marrow cells from congeneic normal catalasemic mice using relatively small numbers of cells following whole body irradiation. The increase in blood catalase activity was physiologically effective as demonstrated by the protection of the previously acatalasemic mice against the otherwise lethal effects of hydrogen peroxide injections. Bone marrow transplantation has the potential to provide a continuous source of some enzymes and may be applicable as treatment for certain congenital enzyme deficiency diseases

  9. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  10. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Warczyńska, Agnieszka; Kwiatkowska, Brygida

    2013-01-01

    Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a “herald” of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted

  11. Bone and bone marrow scintigraphy in the diagnosis of neoplastic involvement of the skeletal system

    International Nuclear Information System (INIS)

    Sacchi, S.; Marietta, M.; Rinaldi, G.; Torelli, U.; Pantusa, M.; Romani, F.; Zaniol, P.

    1987-01-01

    Bone and bone marrow scintigraphy has been performed in 16 patients with epithelial tumor or lymphoproliferative diseases and in 22 patients affected by multiple myeloma. The first technique revealed skeletal alterations in 60.5% of all the patients; the second in 42.1%. In 21 cases, however, there was agreement between bone and bone marrow radionuclide imaging, making possible a more accurate etiological diagnosis of the hot areas found in skeletal scintigraphy. In patients with multiple myeloma we found a high correlation between the marrow distribution pattern and the plasmocytoma staging accoding to Durie and Salmon. It is thoght therefore that bone marrow scintigraphy may be useful sice it provides a further diagnostic tool for a better clinical staging of patients with multiple myeloma

  12. Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

    DEFF Research Database (Denmark)

    Lisse, I; Hasselbalch, H; Junker, P

    1991-01-01

    Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...

  13. Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells

    Directory of Open Access Journals (Sweden)

    Süleyman Coşkun

    2014-10-01

    Full Text Available Hematopoietic stem cells (HSCs reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5, coincident with marrow vascularization, and were contained within the c-Kit+Sca-1+Lin− (KSL population. We used Osterix-null (Osx−/− mice that form vascularized marrow but lack osteolineage cells to dissect the role(s of these cellular components in HSC development. Osx−/− fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.

  14. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells.

    Science.gov (United States)

    Coşkun, Süleyman; Chao, Hsu; Vasavada, Hema; Heydari, Kartoosh; Gonzales, Naomi; Zhou, Xin; de Crombrugghe, Benoit; Hirschi, Karen K

    2014-10-23

    Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    International Nuclear Information System (INIS)

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-01-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT

  16. Bone marrow MRI in patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Chen Zhao; Guo You; Wang Renfa; Zou Mingli; Liu Wenli; Xia Liming; Wang Chengyuan

    2004-01-01

    Objective: To observe the MR imaging of bone marrow in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to reveal the rule of bone marrow infiltration and the role of MRI in diagnosing and predicting the prognosis of myelodysplastic syndromes. Methods: Thirty patients received MRI after the diagnosis based on clinic and FAB subtype study, including 16 with MDS and 14 with AML. MR image was obtained by T 1 -weighted spin echo and shot time inversion recovery in pelvis and femur. The examining results of morphology and blood routine were collected at the same time. 30 age-matched volunteers were selected as controls. Results: The MRI appearance was classified into their patterns based on scope of focus. MRI patterns from grade 1 to grade 3 was observed in patients with MDS. All patients with AML distributed in grade 2 to grade 3. The distribution of patterns had no significant difference between MDS and AML (P>0.05). The marrow ratio had significant difference among MDS, AML, and controls (P<0.05). The MRI grade was consistent with the clinic diagnostic indexes. Conclusion: MRI can provide a better understanding of the difference between MDS and AML. MRI can estimate the extent of disease in the marrow as a whole. MRI of bone marrow can provide imaging basis in diagnosis and predicting the prognosis for patients with MDS

  17. Development, regulation, metabolism and function of bone marrow adipose tissues.

    Science.gov (United States)

    Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

    2018-05-01

    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF

    Science.gov (United States)

    Zhou, Bo O.; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J.; Naveiras, Olaia; Morrison, Sean J.

    2017-01-01

    Endothelial cells and Leptin Receptor+ (LepR+) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including Stem Cell Factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent ~5% of LepR+ cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited hematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR+ cells, but not endothelial, hematopoietic, or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 ‘fatless” mice exhibited delayed hematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes hematopoietic regeneration. PMID:28714970

  19. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

    Science.gov (United States)

    Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

    2017-08-01

    Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

  20. Bone marrow transplantation for treatment of radiation disease. Problems involved

    International Nuclear Information System (INIS)

    Fliedner, T.M.

    1992-01-01

    Transplantation of bone marrow cells still is one of the major means available for treatment of radiation injuries. The decisive indication is the diagnostic of irreversible damage to the hemopoietic stem cells, which becomes manifest about 5 or 6 days after exposure, by severe granulocytopenia and simultaneous, progressive thrombopenia. The radiation dose provoking such severe injury is estimated to be at least 9-10 Gy of homogeneous whole-body irradiation. Preparatory measures for transplantation include proof of tissue compatibility of donor and patient, sufficient immunosuppression prior to and/or after irradiation and bone marrow transplantation. The donor's marrow should be free of T-cells. In spite of preparatory treatment, complications such as immunological reactions or disturbance of organ functions are to be very probable. These are treated according to therapy protocols. (orig./MG) [de

  1. Injection of demineralized bone matrix with bone marrow concentrate improves healing in unicameral bone cyst.

    Science.gov (United States)

    Di Bella, Claudia; Dozza, Barbara; Frisoni, Tommaso; Cevolani, Luca; Donati, Davide

    2010-11-01

    Unicameral bone cysts are benign lesions that usually spontaneously regress with skeletal maturity; however, the high risk of pathologic fractures often justifies treatment that could reinforce a weakened bone cortex. Various treatments have been proposed but there is no consensus regarding the best procedure. We compared the healing rates and failures of two methods of cure based on multiple injections of corticosteroid or a single injection of demineralized bone matrix (DBM) in association with bone marrow concentrate (BMC). We retrospectively reviewed 184 patients who had one of the two treatments for unicameral bone cysts with cortical erosion. Clinical records were reviewed for treatment failures and radiographs for healing in all patients. The minimum followup was 12 months for the Steroids Group (mean, 48 months; range, 12-120 months) and 12 months for the DBM + BMC Group (mean, 20 months; range, 12-28 months). After one treatment we observed a lower healing rate of cysts treated with multiple injections of steroids compared with the healing after the first injection of DBM + BMC (21% versus 58%, respectively). At last followup, 38% healed with steroids and 71% with DBM + BMC. The rate of failure after one steroid injection was higher than after a single injection of BDM + BMC (63% versus 24%, respectively). We observed no difference in fracture rates after treatment between the two groups. A single injection of DBM added with autologous bone marrow concentrate appears to provide a higher healing rate with a lower number of failures compared with a single injection of steroids.

  2. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    International Nuclear Information System (INIS)

    Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

    2008-01-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD 50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  3. Bone marrow scintigraphy with 111In-chloride

    International Nuclear Information System (INIS)

    Fujishima, Mamoru; Hiraki, Yoshio; Takeda, Yoshihiro; Kohno, Yoshihiro; Niiya, Harutaka; Aono, Kaname; Yorimitsu, Seiichi; Takahashi, Isao

    1988-01-01

    Bone marrow scintigraphy with indium chloride ( 111 In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1) in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2) in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3) in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4) four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5) in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific. (author)

  4. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    Science.gov (United States)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  5. Value of Bone marrow Examination in Pyrexia of unknown origin

    Directory of Open Access Journals (Sweden)

    A Jha

    2013-10-01

    Full Text Available Background: Pyrexia of unknown origin is a common diagnostic dilemma. Series of diagnostic modalities are required to arrive at diagnosis. Bone marrow examination is one of the common tests implicated in the diagnosis in combination with other diagnostic modalities. Present study has attempted to explore the causes of pyrexia of unknown origin based on bone marrow morphological study. Materials and Methods: In a one year prospective study conducted at Manipal Teaching Hospital, Pokhara, Nepal; bone marrow aspiration and biopsy was performed and evaluated morphologically, in 57 patients fulfilling the criteria of classic pyrexia of unknown origin. Results: In 42% cases; specific diagnosis could be made and hematological neoplasm was the most common finding followed by megaloblastic anemia, hypoplastic anemia and one case each of hemophagocytosis, malaria and tuberculosis. Acute leukemia was the most frequently encountered hematological malignancy followed by multiple myeloma, chronic myeloid leukemia, essential thrombocythemia and myelodysplastic syndrome. Conclusion: Morphological examination of bone marrow has important role in diagnosis of pyrexia of unknown origin. However, yield of diagnosis can be increased if it is combined with other diagnostic modalities including radiological, microbiological and serological tests. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8991 Journal of Pathology of Nepal (2013 Vol. 3, 447-451

  6. BONE MARROW AND KIDNEY FAT INDEX IN MALE AND FEMALE ...

    African Journals Online (AJOL)

    uvp

    Bone marrow and kidney fat indices in male and female (gravid and non-gravid) ... Determining body condition of game in the field accurately is not easy as it is not ... of Animal Science is available online at http://www.sasas.co.za/sajas.html ...

  7. Bone Marrow Pathology Predicts Mortality in Chronic Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Cheng-Hao Weng

    2015-01-01

    Full Text Available Introduction. A bone marrow biopsy is a useful procedure for the diagnosis and staging of various hematologic and systemic diseases. The objective of this study was to investigate whether the findings of bone marrow studies can predict mortality in chronic hemodialysis patients. Methods. Seventy-eight end-stage renal disease patients on maintenance hemodialysis underwent bone marrow biopsies between 2000 and 2011, with the most common indication being unexplained anemia followed by unexplained leukocytosis and leukopenia. Results. The survivors had a higher incidence of abnormal megakaryocyte distribution P=0.001, band and segmented cells P=0.021, and lymphoid cells P=0.029 than the nonsurvivors. The overall mortality rate was 38.5% (30/78, and the most common cause of mortality was sepsis (83.3% followed by respiratory failure (10%. In multivariate Cox regression analysis, both decreased (OR 3.714, 95% CI 1.671–8.253, P=0.001 and absent (OR 9.751, 95% CI 2.030–45.115, P=0.004 megakaryocyte distribution (normal megakaryocyte distribution as the reference group, as well as myeloid/erythroid ratio (OR 1.054, CI 1.012–1.098, P=0.011, were predictive of mortality. Conclusion. The results of a bone marrow biopsy can be used to assess the pathology, and, in addition, myeloid/erythroid ratio and abnormal megakaryocyte distribution can predict mortality in chronic hemodialysis patients.

  8. white leghorn chimeras based on bone marrow mesenchymal stem

    African Journals Online (AJOL)

    stem cells (BMMSCs), and to assess its immune tolerance based on variations in proportion of ... Keywords: Bone marrow mesenchymal stem cells, Immune tolerance, ... in tissue injury, transplantation, and ..... 0.05, **p < 0.01; (b) expression of the duck gene in different organs .... CD30hi Marek's disease lymphoma cell.

  9. Pain During Bone Marrow Aspiration: Prevalence and Prevention

    NARCIS (Netherlands)

    Vanhelleputte, P.; Nijs, K.A.N.D.; Delforge, M.; Evers, G.; Vanderschueren, S.

    2003-01-01

    The Prevalence, intensity, determinants and prevention of pain during bone marrow aspiration (BMA) in adults are not well defined. In the first part of this prospective study (observational phase), 132 adult hematological patients undergoing BMA after local anesthesia scored the procedural pain by

  10. Bone marrow dysfunction in chronic heart failure patients

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Voors, Adriaan A.; de Boer, Rudolf A.; Schuringa, Jan J.; Klinkenberg, Theo; van der Harst, Pim; Vellenga, Edo; van Veldhuisen, Dirk J.; van Gilst, Wiek H.

    To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment. Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 +/- 6 years, 75% NYHA class >= III, LVEF 32 +/- 6%), and 20 age- and

  11. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...

  12. Body/bone-marrow differential-temperature sensor

    Science.gov (United States)

    Anselmo, V. J.; Berdahl, C. M.

    1978-01-01

    Differential-temperature sensor developed to compare bone-marrow and body temperature in leukemia patients uses single stable amplifier to monitor temperature difference recorded by thermocouples. Errors are reduced by referencing temperatures to each other, not to separate calibration points.

  13. Specific depletion of mature T lymphocytes from human bone marrow

    DEFF Research Database (Denmark)

    Geisler, C; Møller, J; Plesner, T

    1989-01-01

    An effective method for specific depletion of mature T lymphocytes from human bone marrow mononuclear cells (BMMC) with preservation of prethymic T cells and natural killer (NK) cells is presented. The BMMC were incubated with F101.01, a monoclonal antibody recognizing an epitope of the T...

  14. Bone marrow in pediatric patients with Hodgkin's disease.

    Science.gov (United States)

    Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

    2012-01-01

    Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

  15. HLA Typing for Bone Marrow Transplantation

    Science.gov (United States)

    2011-07-21

    ASBMT American Society for Blood and Marrow Transplantation ASEATTA Australasian and South East Asian Tissue Typing Association ASH American...for investigators to obtain statistical and data management support for prospective trials focusing on addressing various transplant issues. These...these relationships so that when an event occurs no one will need to exchange business cards, but rather will already know who to call. Two levels

  16. Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Beatriz Cesar

    2011-01-01

    Full Text Available A homeopathic complex medication (HCM, with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now report in vivo immunophenotyping of total bone marrow cells and ex vivo effects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measured in vitro. After in vivo treatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects of ex vivo HCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were induced in vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products.

  17. Efficiency of rat bone marrow-derived endothelial progenitor cells on VEGF and SDF-1 expression with the aid of Tanshinone ⅡA%丹参酮ⅡA增效大鼠骨髓源性内皮祖细胞VEGF、SDF-1表达

    Institute of Scientific and Technical Information of China (English)

    杨彦; 陈庆伟; 曹广煜; 李桂琼

    2012-01-01

    Objective:To investigate the effect of rat bone marrow-derived endothelial progenitor cells on VEGF expression with the aid of Tanshinone ⅡA.Methods:The mononuclear cells were isolated from rat femoral and tibial bone marrow using percoll density gradient centrifugation,then induced with vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) and epidermal growth factor(EGF)for two weeks.The expression of cell markers was assessed by immunocytochemistry,and the attached cells were stained with Dil-acLDL and FITC-UEA-1.Then this study included two groups: EPCs and EPCs+ Tanshinone ⅡA groups.The expression levels of VEGF and SDF-1 was detected by fluorescent qRT-PCR and western blot.Results:Compared with the EPCs group,EPCs+ Tanshinone IIA group had a higher VEGF and SDF-1 expression(P0.05).Conclusions:EPCs can increase VEGF and SDF-1 expression with combination of Tanshinone IIA.Homing rate and repairing efficacy of EPCs can improve also with the aid of Tanshinone IIA.EPCs can increase VEGF and SDF-1 expression in injured myocardium after homing,thus improve angiogenesis efficiently.%目的:研究在丹参酮ⅡA的辅助下,骨髓源性内皮祖细胞(EPCs)VEGF与SDF-1表达是否能增强,从而促进细胞归巢。方法:Percoll密度梯度离心法分离SD大鼠骨髓单个核细胞,血管内皮生长因子(VEGF)、表皮生长因子((EGF)、碱性成纤维细胞生长因子(bFGF)诱导培养,并进行形态学、免疫学(免疫细胞化学染色)、功能学(Dil-acLDL与FITC-UEA-1双荧光染色)鉴定。将鉴定为EPCs的细胞分为单纯EPCs组(对照组)、EPCs+丹参酮ⅡA组(加药组)。细胞培养第9d,Western blot与实时荧光定量PCR检测各组VEGF、SDF-1基因与蛋白表达。结果:EPCs+丹参酮IIA组VEGF、SDF-1基因与蛋白表达均高于EPCs组(p均〈0.05)。结论:丹参酮ⅡA可上调大鼠骨

  18. Scintigraphic findings of bone and bone-marrow and determination of bone mineral density using photon absorptiometry in osteopetrosis

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Morita, Koichi

    1988-01-01

    On a 15-year-old girl with osteopetrosis, bone and bonemarrow scintigraphy were performed. Also, bone mineral density (BMD) with quantitative CT (QCT), single photon absorptiometry (SPA) and dual photon absorptiometry (DPA) were measured. On bone scintigraphy the diffusely increased skeletal uptake and relatively diminished renal uptake were noted. On the other hand, on bone marrow scintigraphy poor accumulation in central marrow and peripheral expansion were shown. BMD value by QCT and DPA (mainly trabecular bone) was markedly high, while BMD by SPA (mainly cortical bone) was within normal range. Thus, it was shown that bone and bone-marrow scintigraphy combined with BMD measurement by photon absorptiometry were useful and essential in evaluating the pathophysiology of osteosclerosis. (author)

  19. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  20. Differentiation of B and T lymphocytes from precursor cells resident in the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Rosse, C; Press, O W

    1978-01-01

    A series of experiments in guinea pigs and mice established that proliferating progenitor cells for B and T lymphocytes are a resident population in the bone marrow. It was shown by the combined use of /sup 3/H-TdR radioautography and fluorescent-antibody staining of B and T cells that the majority of bone marrow (BM) lymphocytes are rapidly renewed (RR) B cells and null cells, whereas the thymus (THY) consists overwhelming of RR T lymphocytes; in spleen (SPL) and lymph node (LN) slowly renewed (SR) T and B cells predominate. The rate of B cell turnover in guinea pig bone marrow exceeds that in the SPL or LN, and the appearance of newly generated B cells in the SPL lags behind that in the BM. When systematically administered /sup 3/H-TdR was excluded by tourniquets from tibial and femoral BM no labeled B cells appeared in tibial or femoral marrow over 72 h. When tibial and femoral BM was labeled selectively with /sup 3/H-TdR, labeled B cells appeared in the SPL and LN over 72 h. (It was found in CBA mice that BM cell fractions enriched in lymphocytes (BML) responded to the T cell mitogen PHA in a manner qualitatively different from the response of SPL and LN cells. Experiments with athymic nude mice and with complement-mediated lysis of T and B cells established that PHA responsive cells in SPL and LN were T cells but in BML they were null lymphocytes. Target cells of PHA in BML responded to the mitogen by the generation of T-cell surface markers and blastogenesis; therefore they were identified as pre-T cells. BM pre-T cells are rapidly renewed and, in contrast to PHA responsive cells of SPL and LN, do not recirculate from blood to lymph. Both B and pre-T cells in the BM are division products of transitional cells. Among transitional cells of the marrow are included the progenitors of B and T lmyphhocytes and of all other types of hemopoietic cells.

  1. The emerging role of bone marrow adipose tissue in bone health and dysfunction.

    Science.gov (United States)

    Ambrosi, Thomas H; Schulz, Tim J

    2017-12-01

    Replacement of red hematopoietic bone marrow with yellow adipocyte-rich marrow is a conserved physiological process among mammals. The extent of this conversion is influenced by a wide array of pathological and non-pathological conditions. Of particular interest is the observation that some marrow adipocyte-inducing factors seem to oppose each other, for instance obesity and caloric restriction. Intriguingly, several important molecular characteristics of bone marrow adipose tissue (BMAT) are distinct from the classical depots of white and brown fat tissue. This depot of fat has recently emerged as an active part of the bone marrow niche that exerts paracrine and endocrine functions thereby controlling osteogenesis and hematopoiesis. While some functions of BMAT may be beneficial for metabolic adaptation and bone homeostasis, respectively, most findings assign bone fat a detrimental role during regenerative processes, such as hematopoiesis and osteogenesis. Thus, an improved understanding of the biological mechanisms leading to formation of BMAT, its molecular characteristics, and its physiological role in the bone marrow niche is warranted. Here we review the current understanding of BMAT biology and its potential implications for health and the development of pathological conditions.

  2. Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM : Bone marrow derived cell in GBM

    NARCIS (Netherlands)

    Boer, Jennifer C.; Walenkamp, Annemiek M. E.; den Dunnen, Wilfred F. A.

    2014-01-01

    Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for

  3. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo.

    Science.gov (United States)

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo . Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Low frequency (25-50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  4. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    Directory of Open Access Journals (Sweden)

    Shengwei He

    2017-01-01

    Full Text Available Objective(s:To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods:Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligan, and pre-collagen type 1 a were measured. Results:Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligand, and pre-collagen type 1 a were also markedly higher following 25 and 50 Hz treatment. Conclusion:Low frequency (25–50 Hz vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  5. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

    Science.gov (United States)

    Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

    2008-02-01

    The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

  7. Bone marrow MR imaging findings in disuse osteoporosis

    International Nuclear Information System (INIS)

    Abreu, Marcelo R. de; Wesselly, Michelle; Chung, Christine B.; Resnick, Donald

    2011-01-01

    To demonstrate MR imaging findings in the cortical and trabecular bone as well as marrow changes in patients with disuse osteoporosis (DO). Sixteen patients (14 men, 2 women, aged 27-86 years) with clinical and radiographic evidence of DO of a lower limb joint (10 knees, 6 ankles) with MR examination of the same joint performed within a 1-month period were selected, as well as 16 healthy volunteers (7 men, 9 women, aged 25-75 years, 10 knees and 6 ankles). MR imaging findings of the bone marrow were analyzed by 2 musculoskeletal radiologists in consensus regarding: diffuse or focal signal alteration, reinforcement of vertical or longitudinal trabecular lines, and presence of abnormal vascularization. All patients (100%,16/16) with DO presented MR imaging abnormalities of the bone marrow, such as: accentuation of vertical trabecular lines (50%, 8/16), presence of subchondral lobules of fat (37.5%, 6/16), presence of horizontal trabecular lines (31%, 5/16), prominence of bone vessels (25%, 4/16), and presence of dotted areas of high signal intensity on T2-weighted fat-suppressed sequences (12.5%, 2/16). Such MR findings did not appear in the control individuals. There are several MR imaging findings in bones with DO that range from accentuation of vertical and horizontal marrow lines, presence of subchondral lobules of fat, prominent bone vascularization and the presence of dotted foci of high signal intensity on T2-weighted fat-suppressed sequences. Recognition of these signs may prove helpful in the identification of DO as well as distinguishing these findings from other entities. (orig.)

  8. Migration of bone marrow cells to the thymus in sublethally irradiated mice

    International Nuclear Information System (INIS)

    Varlet, Andree; Lenaerts, Patrick; Houben-Defresne, M.P.; Boniver, Jacques

    1982-01-01

    In sublethally irradiated mice, thymus repopulation is due first to the proliferation of surviving thymocytes followed by the multiplication of bone marrow derived prothymocytes. The migration of bone marrow cells to the thymus after a single sublethal whole-body X irradiation was studied by using fluorescein isothiocyanate as a cell marker. Irradiation increases the permissiveness of the thymus to the immigration of bone marrow cells. Furthermore, the post-Rx regenerating bone marrow cells exhibit migration capacities greater than the normal ones. The radiation induced changes in the bone marrow thymus interaction might play an important role in thymus regeneration after sublethal irradiation [fr

  9. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-01-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  10. BONE MARROW BIOPSY IN EVALUATION OF HAEMATOLOGICAL DISORDERS

    Directory of Open Access Journals (Sweden)

    Sandhya Rani Sahoo

    2017-04-01

    Full Text Available BACKGROUND Bone Marrow Trephine Biopsy (BMTB and aspiration is critical for diagnosis, prognostic evaluation and monitoring therapeutic response. BMTB is of greater value in assessing cellularity, degree of fibrosis, marrow architecture and especially when aspiration is dry tap. At the same time, it provides sample for immunohistochemistry. MATERIALSAND METHODS It is a single centre observational study conducted from July 2014 to July 2016 in Department of Pathology, S.C.B. Medical College, Cuttack, which included both cell block and touch imprint along with trephine biopsy. Cases selected where lymphoma studied for pattern and extent of infiltration. Aspiration with dry tap and selected cases of myeloproliferative disorders, myelodysplastic syndrome, leukaemia (both acute and chronic, anaemia, multiple myeloma were studied. Jamshidi needle was used for biopsy. Samples obtained were formalin preserved, kept in decalcification solution (Hammersmith protocol and H and E slides prepared. Special stain-like reticulin and Masson’s trichrome were used for grading of fibrosis. Immunohistochemistry was done on selected cases of lymphoma. RESULTS Out of total 100 cases studied, 60 were of haematopoietic and lymphoid neoplasms, 12 anaemia, 20 secondary metastasis, 8 miscellaneous (1 haemophagocytic lymphohistiocytic disease, 1 storage disease, 1 granulomatous and 5 ITP. CONCLUSION The study was conducted to establish the advantage of bone marrow biopsy in inadequate and failed aspiration, but both are complementary to each other and together provide a comprehensive evaluation of the bone marrow. Bone marrow fibrosis are well accessed and increased detection of tumour cells in suspected secondary metastasis. Special stains, IHC, cytogenetic study can be done over biopsy block.

  11. Factors controlling the engraftment of transplanted dog bone marrow cells

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Klapwyk, W.M.; Heidt, P.J.; Hogeweg, B.; Zurcher, C.; Bekkum, D.W. van

    1982-01-01

    The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrme was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility comples (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rateof hemopoietic recovery correlated with the number of BM cells given. Approximtely 2 x 10 7 autologous and 1 x 10 8 MHC identical BM cells.kg -1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterine inertia in female dogs after 7.5 GY TBI. Fertility in males or females was not changed by radiation. An increase of pancreas fibrosis was noted in dogs receiving fractions of 6.0 Gy TBI. (author)

  12. Transition pattern and mechanism of B-lymphocyte precursors in regenerated mouse bone marrow after subtotal body irradiation.

    Directory of Open Access Journals (Sweden)

    Deping Han

    Full Text Available Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI, the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1-2 weeks after irradiation, but no change occurred after 3-4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1-2 weeks after sub-TBI but increased dramatically after 3-4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.

  13. Individual differences in post radiation regeneration of the bone marrow in nonuniform irradiation (experimental investigation)

    International Nuclear Information System (INIS)

    Kalandarova, M.P.

    1980-01-01

    Reparative regeneration in bone marrow of sternum and iliac bone in each of 20 dogs was studied after single and two-time total X-ray irradiation. Extreme dose rates in bodies differed 5 and 8 times. It was shown that bone marrow repair did not depend on its composition before irradiation. Dogs whose bone narrow was rich of cellular elements before irradiation had both active and sharply reduced bone marrow regeneration after single and two-time irradiation in 0.75-1.45 Gy doses (sternum). Animals with a poor total cellular composition of bone marrow of sternum before irradiation also had differences in the course of reparative processes: in some of them they were considerably pronoUnced and in others bone marrow aplasia lasted for one month. IndiVidual differences in the bone marrow (iliac bone) irradiated with 1.85-3.2 Gy doses were less marked during the reparative regeneration

  14. The capacity of peripheral blood stem cells mobilised with chemotherapy plus G-CSF to repopulate irradiated marrow stroma in vitro is similar to that of bone marrow

    International Nuclear Information System (INIS)

    Demuynck, H.; Dexter, T.M.; Testa, N.G.; Pettengell, R.; Campos, E. de

    1992-01-01

    After treatment of patients with intermediate or high grade non-Hodgkin lymphoma with chemotherapy plus G-CSF the numbers of haemopoietic progenitor cells in the circulation increased to a mean of 226-fold for mixed CFC (Mix-CFC), 278-fold for GM-CFC and 29-fold for erythroid burst forming unit (BFU-E). The mean increase was modest (7-12-fold) for patients treated with chemotherapy alone. Peripheral blood mononuclear cells harvested at the time of the peak in the numbers of progenitors, or 2-4 days before the peak, seeded onto irradiated marrow stroma in vitro, repopulated the stroma and generated active haemopoiesis at least as effectively as bone marrow cells on a cell per cell basis. This is in contrast to the poor repopulating capacity of pretreatment blood. The results indicate that not only the progenitor cells, but also the repopulating stem cells migrated into the blood after chemotherapy plus G-CSF in sufficient numbers to allow harvesting and successful grafting without the possible complication of late haemopoietic failure. (author)

  15. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

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    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    2000-10-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

  16. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    International Nuclear Information System (INIS)

    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo

    2000-01-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean ±S.D.: 0.87±0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean ±S.D.: 0.34±0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean ±S.D. 1.35±0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean ±S.D.: 3.50±2.51 %/min vs. 7.13±1

  17. Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Carsten, A.L.; Brecher, G.; Feinendegen, L.

    1979-01-01

    Studies were conducted on the appearance of cells in recipient bone marrow with chromosome markers after bone marrow transfusion to recipients that had different treatments. Investigators tried to replete the bone marrow CFV spleen at various times after recovery from maximal sublethal doses of x radiation or during continuous exposure to tritiated water. Studies were made on the effect of diverse treatments on the acceptance of bone marrow transfusions as shown by chromosomal markers. Results showed that the bone marrow of animals rescued by transfusion of 4 x 10 6 bone marrow cells will accept from 0 to 25% of the second transfusion of bone marrow cells given one to 4 months after the first transfusion and examined 2 to 3 weeks after the second transfusion. This may be due to the second transfusion filling up empty niches

  18. Evidence of homing of each fraction of bone marrow cells after scheduled transplantation in mice

    International Nuclear Information System (INIS)

    Sun Suping; Cai Jianming; Xiang Yingsong; Huang Dingde; Zhao Fang; Gao Jianguo; Yang Rujun

    2003-01-01

    Objective: To identify homing of bone marrow cells after every fractionation during scheduled transplantation. Methods: The recipient mice were transplanted with homologous (H-2K d ) and allogeneic (H-2K b ) mouse bone marrow cells after lethal irradiation, and the homing status of allogeneic bone marrow cells in host bone marrow and spleen was observed. Results: A quantity of allogeneic homed cells were observed in host bone marrow, and the percentage of homing cells in second fraction was the highest in all groups (P<0.01). The allogeneic homed cells in spleen declined along with increase of the number of fraction, suggesting that regulation of homing to spleen was different from that to bone marrow. Conclusion: In scheduled bone marrow transplantation niche may be more effectively utilized and thus transplantation efficiency be enhanced

  19. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  20. Effect of superparamagnetic iron oxide on bone marrow

    International Nuclear Information System (INIS)

    Hundt, W.; Helmberger, T.; Reiser, M.; Petsch, R.

    2000-01-01

    The goal of this study was to compare the effects of SPIO particles on the signal intensity of the bone marrow of the vertebra spine in patients with and without liver cirrhosis. Forty-eight patients with normal liver tissue and 56 patients with liver cirrhosis were examined before and after intravenous SPIO administration, using a 1.5-T system (Magnetom Vision, Siemens, Erlangen, Germany) with a semiflexible cp-array coil. Three different pulse sequences were applied: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression and a T2 * -weighted gradient-echo sequence. The signal-to-noise ratio (SNR) of the liver, vertebra bone and paraspinal muscle were obtained. The SNR value change in each patient group and the SNR value difference between the two groups were evaluated. For assessment of statistical significance, Student's t-test with a level of p * -weighted gradient-echo sequence, the signal intensity decrease of the normal liver tissue was approximately -65.6 % (p = 0.00), in cirrhotic liver tissue the decrease was -29.9 % (p = 0.02). The SNR values of the bone marrow showed a decrease of -27.8 % (p = 0.04) in the noncirrhotic liver group, whereas in the cirrhotic liver group it was only -11.3 % and statistically not significant. The effect of SPIO particles on the liver and bone marrow is significantly less in patients with liver cirrhosis. (orig.)

  1. Transcriptome analysis of bone marrow mesenchymal stromal cells from patients with primary myelofibrosis

    Directory of Open Access Journals (Sweden)

    Christophe Martinaud

    2015-09-01

    Full Text Available Primary myelofibrosis (PMF is a clonal myeloproliferative neoplasm whose severity and treatment complexity are attributed to the presence of bone marrow (BM fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironmental niches. Within these niches, mesenchymal stromal cells (BM-MSC play a hematopoietic supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic stem/progenitor cells. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic stem/progenitor cell deregulation that features PMF.

  2. Peritumoral bone marrow edema accompanying benign giant cell tumor

    International Nuclear Information System (INIS)

    Kim, Sung Hun; Park, Jeong Mi; Kim, Ji Yong; Gi, Won Hee; Sung, Mi Suk; Lee, Jae Mun; Shin, Kyung Sub

    1998-01-01

    To evaluate the frequency of peritumoral bone marrow(BM) edema accompanying benign giant cell tumor(GCT) of the appendicular bone by magnetic resonance(MR) imaging and to correlate MRI findings with those of plain radiography and bone scintigraphy. Eighteen cases of pathologically proven benign GCT of the appendicular bone were retrospectively analyzed using MR images, plain radiographs and bone scintigrams. A plain radiography was available in 15 cases, and a scintigram in six. Marrow edema was defined as peritumoral signal changes which were of homogeneous intermediate or low signal intensity(SI) onT1WI and high SI on T2WI, relative to the SI of normal BM, and homogeneous enhancement on Gd-DTPA -enhanced T1WI. The transition zone, sclerotic margin and aggressiveness of the lesion were assessed on the basis of plain radiographs. BM edema seen on MR images was correlated with plain radiographic and scintigraphic findings. 1. Peritumoral BM edema was seen on MR images in 10 of 18 cases (55.5%). 2. In 8 of 15 cases for which plain radiographs were available, MR imaging revealed BM edema. In six of these eight, transition zone was wide, while in two it was narrow. Six of seven patients without marrow edema showed a wide transition zone, and in one this was narrow. There was significant correlation between BM edema shown by MR imaging and the transition zone seen on plain radiographs (x 2 , p<0.05). But the aggressiveness shown by plain radiographs correlated only marginally while the presence of sclerotic rim did not correlate. 3. All six cases for which a bone scintigram was available showed an extended uptake pattern. In five of the six, MR imaging revealed edema. Peritumoral BM edema was frequently seen (55.5%) in the GCTs of appendicular bone; it was more often shown in association with a wide transition zone by plain radiographs.=20

  3. Influence of intensity of bone marrow erythropoietic activity on radiosensitivity of mice. Part 2. Effects of carbon monoxide induced hypererythropoiesis and polycythemia on ability of bone marrow to restitute erythropoiesis in irradiated recipients

    International Nuclear Information System (INIS)

    Kwiek, S.

    1986-01-01

    Hypererythropoiesis was induced in mice by exposure to carbon monoxide, and they got polycythemic after transfer to normal air. Erythropoietic repopulation ability (ERA) of transplanted bone marrow decreased to one-third by day 6 of carbon monoxide hypoxia, and returned to normal level during subsequent polycythemia. These changes did not correlate with alteration of CFU-S counts. The found discrepances are ascribed to lack of unipotential erythroid progenitor cells in hypererythropoietic bone marrow. Possibility of assessment of the part of ERA due to the latter cells on the basis of parallel determinations of ERA and CFU-S counts in polycythemic and hypererythropoietic or normal mice is discussed. Complete lack of endogenous haemopoietic macrocolonies was noted in irradiated polycythemic mice. The cells constituting the cellular basis of ERA were found to be insensitive to hydroxyurea. 13 refs., 3 tabs. (author)

  4. Analysis of bone marrow plasma cells in patients with solitary bone plasmacytoma.

    Science.gov (United States)

    Bhaskar, Archana; Gupta, Ritu; Sharma, Atul; Kumar, Lalit; Jain, Paresh

    Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (κ) FITC and anti-lambda (λ) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The κ:λ ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy.

  5. Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates.

    Science.gov (United States)

    Gori, Jennifer L; Butler, Jason M; Kunar, Balvir; Poulos, Michael G; Ginsberg, Michael; Nolan, Daniel J; Norgaard, Zachary K; Adair, Jennifer E; Rafii, Shahin; Kiem, Hans-Peter

    2017-03-01

    Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34 + cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates. CD34 + C38 - HSPCs cocultured with ECs expanded up to 17-fold, with a significant increase in hematopoietic colony-forming activity compared with cells cultured with cytokines alone (colony-forming unit-granulocyte-erythroid-macrophage-monocyte; p < .005). BM CD34 + cells that were transduced with green fluorescent protein lentivirus vector and expanded on ECs engrafted long term with multilineage polyclonal reconstitution. Gene marking was observed in granulocytes, lymphocytes, platelets, and erythrocytes. Whole transcriptome analysis indicated that EC coculture altered the expression profile of 75 genes in the BM CD34 + cells without impeding the long-term engraftment potential. These findings show that an ex vivo vascular niche is an effective platform for expansion of adult BM HSPCs. Stem Cells Translational Medicine 2017;6:864-876. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  6. Endothelial Cells Promote Expansion of Long‐Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates

    Science.gov (United States)

    Gori, Jennifer L.; Butler, Jason M.; Kunar, Balvir; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Norgaard, Zachary K.; Adair, Jennifer E.; Rafii, Shahin

    2016-01-01

    Abstract Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self‐renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self‐renewal. To test this hypothesis, BM autologous CD34+ cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates. CD34+C38− HSPCs cocultured with ECs expanded up to 17‐fold, with a significant increase in hematopoietic colony‐forming activity compared with cells cultured with cytokines alone (colony‐forming unit‐granulocyte‐erythroid‐macrophage‐monocyte; p < .005). BM CD34+ cells that were transduced with green fluorescent protein lentivirus vector and expanded on ECs engrafted long term with multilineage polyclonal reconstitution. Gene marking was observed in granulocytes, lymphocytes, platelets, and erythrocytes. Whole transcriptome analysis indicated that EC coculture altered the expression profile of 75 genes in the BM CD34+ cells without impeding the long‐term engraftment potential. These findings show that an ex vivo vascular niche is an effective platform for expansion of adult BM HSPCs. Stem Cells Translational Medicine 2017;6:864–876 PMID:28297579

  7. Late renal dysfunction in adult survivors of bone marrow transplantation

    International Nuclear Information System (INIS)

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E.

    1991-01-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction

  8. Juvenile xanthogranuloma with clonal proliferation in the bone marrow.

    Science.gov (United States)

    Mały, Ewa; Przyborska, Marta; Rybczyńska, Aleksandra; Konatkowska, Benigna; Nowak, Jerzy; Januszkiewicz, Danuta

    2012-04-01

    The triple association between juvenile xanthogranuloma (JXG), juvenile myelomonocytic leukemia and neurofibromatosis was described in literature in about 20 cases. In this paper, the case of an 11-month-old infant boy with a disseminated JXG with unusual cytogenetic representation in the bone marrow was reported. Neurofibromatosis and juvenile myelomonocytic leukemia were excluded, just the same as other leukemias. Bone marrow and peripheral blood cytogenetic analysis revealed a karyotype with many rearrangements 46,XY,-6,der(12)t(6;12)(p21;p13),del(7)(p13p22),+9 once described in the literature as a B-acute lymphoblastic leukemia case. On the contrary, in our patient immunologic testing demonstrated a high activity of T lymphocytes, however, inflammation was excluded. To the best of our knowledge this is the first described case of systemic JXG with determined karyotype representing unusual chromosomal aberrations.

  9. CHORD simulation for insult assessment to the red bone marrow

    International Nuclear Information System (INIS)

    Jones, T.D.

    1976-09-01

    Critical Human Organ Radiation Dosimetry (CHORD) probability density functions for A-P, P-A, bilateral, rotational, and isotropic incidence, plus simple depth-dose data, permit the rapid estimation of the radiation insult to the active red bone marrow system of the ICRP Reference Man. The CHORD concept follows the variations in the microscopic processes of absorption, attenuation, and scattering on a macroscopic level so that it is not necessary to attempt detailed calculations for each and every case of interest. Similar techniques have been applied to reactor criticality calculations and the general logic of the CHORD process can be applied to any cause-response type situation which can be described in terms of variation with distance in the medium of interest. Doses to active bone marrow from exposures to photons and neutrons are presented and excellent agreement is shown with the few available experimental results

  10. Quantitative MR imaging of normal and leukemic bone marrow

    International Nuclear Information System (INIS)

    Hinks, R.S.; Dunlap, H.J.; Poon, P.Y.; Curtis, J.; Henkelman, R.M.

    1986-01-01

    The authors have developed and tested a protocol that allows extraction of reliable T1 and T2 relaxation times from imaging data. They have used these methods to study in vivo the bone marrow of healthy volunteers and patients with acute leukemia. Examinations were performed at 6.25 MHz using an interleaved ISE/SE sequence to calculate T1 and an eight echo (TE = 25) sequence to calculate T2. The results are summarized as follows: In leukemic patients, T1 = 476 +- 115 msec; in leukemic patients in remission, T1 = 290 +- 31 msec; in healthy volunteers, T1 = 329 +- 32 msec. The T2 values were not significantly different for the three groups (105 +- 10 msec). Work is underway to evaluate whether T1 values of bone marrow may be used to monitor patients in remission and to detect the onset of relapse

  11. Neuromyelitis optica in an adolescent after bone marrow transplantation.

    Science.gov (United States)

    Baumer, Fiona M; Kamihara, Junne; Gorman, Mark P

    2015-01-01

    Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes. We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis. Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Bone marrow blood vessels: normal and neoplastic niche

    Directory of Open Access Journals (Sweden)

    Saeid Shahrabi

    2016-11-01

    Full Text Available Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016 of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases.

  13. Bone marrow hypoplasia associated with fenbendazole administration in a dog.

    Science.gov (United States)

    Gary, Anthony T; Kerl, Marie E; Wiedmeyer, Charles E; Turnquist, Susan E; Cohn, Leah A

    2004-01-01

    A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.

  14. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  15. Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

    Science.gov (United States)

    Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

    2018-04-01

    Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

  16. Radiation dose to trabecular bone marrow stem cells from 3H, 14C and selected α-emitters incorporated in a bone remodeling compartment

    International Nuclear Information System (INIS)

    Nie Huiling; Richardson, Richard B

    2009-01-01

    A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for 3 H, 14 C and a set of α-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 μm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 μm endosteum for 3 H, 14 C and α-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal α-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

  17. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

    DEFF Research Database (Denmark)

    Tormin, Ariane; Li, Ou; Brune, Jan Claas

    2011-01-01

    Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of prim...

  18. A patient with familial bone marrow failure and an inversion of chromosome 8.

    Science.gov (United States)

    Buchbinder, David Kyle; Zadeh, Touran; Nugent, Diane

    2011-12-01

    Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed.

  19. Bone marrow reconstitution of immune responses following irradiation in the leopard frog, Rana pipiens

    International Nuclear Information System (INIS)

    Ramirez, J.A.; Wright, R.K.; Cooper, E.L.

    1983-01-01

    The bone marrow of Rana is an important source of cells capable of maintaining individual viability, responding to Concanavalin A (Con A) and producing PFC against sheep erythrocyte (SRBC) antigens. Frog marrow is more effective than the spleen in maintaining life. Radiation destroys the ability of frogs to respond to SRBC immunization (lack of bone marrow and spleen PFC, serum antibody) and bone marrow/spleen cells to respond to Con A, i.e., bone marrow and spleen contain radiation-sensitive cells. Shielding one hind leg during irradiation leads to reconstitution of bone marrow/spleen PFC responses, antibody synthesis and individual viability. Our results suggest that bone marrow is: a) the source of stem cells, and b) the source of mature T- and B- lymphocytes that can recirculate within the immune system

  20. Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

    International Nuclear Information System (INIS)

    Macias Abraham, Consuelo; Valle Perez, Lazaro O del; Baganet Cobas, Aymara

    2011-01-01

    Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90 +c ells in mononuclear cells from CD34 -/ CD45 -p eripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34 +c ells in peripheral blood stem cells with a low expression of molecules CD117 -a nd DR -s uggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

  1. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  2. Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

    Directory of Open Access Journals (Sweden)

    Muhury Manas

    2009-10-01

    Full Text Available Context: Dysplastic changes are well documented in myelodysplastic syndromes (MDS. However, they are also observed in non-MDS hematological conditions. Aims: To evaluate the megakaryocytic alterations in the bone marrow aspirations in cases of non-MDS related thrombocytopenia. Setting and Design: A prospective study of 144 bone marrow aspirates was conducted in the department of pathology, Kasturba Medical College, Mangalore. The aspirates were studied to assess the number and morphology of the megakaryocytes in non-MDS related thrombocytopenia and evaluate their significance when compared to changes in MDS. Materials and Methods: The bone marrow aspiration smears were stained with Leishman stain and examined under light microscope. Statistical Analysis Used: Fisher′s exact test. A P value less than 0.05 was considered significant. Sensitivity and specificity was calculated for those features which were significant in the relevant hematological disorders. Results: The sensitivity of immature megakaryocytes, dysplastic forms and micromegakaryocytes in cases of immune thrombocytopenic purpura was 100%, 89% and 42% respectively. The specificity of emperipolesis was 74%. In cases of infection-associated thrombocytopenia, immature megakaryocytes had a sensitivity of 100% and cytoplasmic vacuolization were 86% specific. The sensitivity of the dysplastic forms in megaloblastic anemia was 75%. However, no platelet budding was observed. The presence of micromegakaryocyte had a specificity of 83% in MDS, and was statistically significant when compared to cases of non-MDS conditions (P< 0.05. Conclusions: Careful understanding of the morphological changes of megakaryocytes in bone marrow aspirates can improve the diagnostic accuracy for a wide range of hematological disorders thereby enabling proper therapeutic interventions.

  3. Effect of salidroside on radiation-induced bone marrow adipogenesis

    International Nuclear Information System (INIS)

    Zhu Jincan; Chen Xiaoyu; Liu Chengcheng; Zhu Aizhen; Liu Shantao; Liu Gexiu

    2014-01-01

    Objective: To investigate the potential and underlying molecular mechanism of salidroside in ameliorating radiation-induced bone marrow adipogenesis and stimulating hematopoiesis. Methods: The female BALB/c mice aged 6-7 weeks were randomly divided into normal control group, radiation group and salidroside group. The radiation group and salidroside group were irradiated with 6.0 Gy of "6"0Co γ-rays. The salidroside group was intraperitoneally injected with 30 mg·kg"-"1·d"-"1 salidroside at 12 h and then every day until 8th d after radiation. The normal control group and radiation group were treated with equal volume of saline as control of salidroside. At 14 d after radiation, the mice weight, peripheral blood count, femur bone marrow histology, and the proportion of adipocyte area were measured, and the expressions of PPAR-γ and FABP4 were detected by q-PCR. Results: After irradiation, the numbers of white blood cells, hemoglobin and platelet in peripheral blood were reduced obviously, and the percentage of adipocyte area was increased significantly. Compared with mice in the radiation group, salidroside inhibited adipogenesis and reduced the proportion of adipocyte area (t = 13.31, P < 0.05) by reducing the expressions of PPAR-γ and FABP4 (t = 8.64, 13.19, P < 0.05). The number of white blood cells was partly recovered at 7 d after irradiation (t = 5.80, P < 0.05). Both white blood cells and hemoglobinin in peripheral blood of the salidroside group were higher than those in the radiation group at 14 d after irradiation. Conclusions: Salidroside could inhibit radiation-induced bone marrow adipogenesis and regulate bone marrow microenvironment, thereby promotes hematopoietic recovery in mice after radiation injury. (authors)

  4. Hematological effects: comparative studies on the radiation survival characteristics in vivo and in vitro of bone marrow-derived clonogenic populations (CFU-C and PFU-C) and some observations on bone marrow cellularity in beagles

    International Nuclear Information System (INIS)

    Wilson, F.D.; O'Grady, L.; Momeni, M.; Wheeling, J.A.; Klein, K.; Graham, R.; Jow, N.; Di Bartola, S.

    1975-01-01

    Data accumulated for the hematological effects program are reviewed. Particular emphasis is given to the effects of acute and chronic irradiation on hematopoietic progenitor populations (CFU-C, colony-forming units in culture) and ''candidate'' mesenchymal progenitors (PFU-C, plaque-forming units in culture) using methylcellulose bone marrow culture systems and both in vivo and in vitro radiation exposure protocols. Preliminary results of studies on the temporal effects of acute x-irradiation on the capacity of PFU-C to generate colony stimulating activity (CSA) are also presented. The results of such experiments are providing the basis upon which future RBE studies on a variety of nuclides will be structured. Data (including age related changes) is also presented on in vivo bone marrow cellularity determinations, as well as for marrow stem cell quantitative studies using nondestructive techniques for normal Beagles. In these studies, two techniques for correction of variable effects of hemodilution are compared. Such studies are also providing baseline data for the 60 Co hematological effects program

  5. Evaluation of lumbar vertebral bone marrow changes with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kakitsubata, Yousuke; Nabeshima, Kazuki; Kakitsubata, Sachiko; Watanabe, Katsushi (Miyazaki Medical Coll., Kiyotake (Japan))

    1993-11-01

    Seven hundred nine magnetic resonance (MR) imaging studies of the lumbar spine were reviewed to assess the signal intensity (SI) changes in vertebral bone marrow. Marrow changes were classified into four types according to their SI changes on T1-weighted images (T1-WI) and T2-WI. Type 1 changes (decreased SI on T1-WI and increased SI on T2-WI) were identified in 28 patients (3.9%), type 2 changes (increased SI on T1-WI and isointense or slightly increased SI on T2-WI) in 184 (26%), type 3 changes (decreased SI on both T1-WI and T2-WI) in 71 (10%), and type 4 changes (linearly increased SI on T1-WI in the center of the vertebral body) in 142 (20%). Plain radiographs showed sclerotic changes in patients with type 3. In patients with type 1 or 4 changes, no focal abnormalities were observed. Histological evaluation of type 1 change revealed fibrous tissue including cartilaginous formation. Focal replacement by fatty tissue was observed in type 2 and type 4 changes. Bone sclerosis was observed in type 4 change. Type 1, type 2 and type 3 changes, which occurred commonly in the old and in the lower lumbar level, appear to reflect a spectrum of degenerative changes of the bone marrow including both pathological and physiological ones. (author).

  6. FANCD2 protects against bone marrow injury from ferroptosis

    International Nuclear Information System (INIS)

    Song, Xinxin; Xie, Yangchun; Kang, Rui; Hou, Wen; Sun, Xiaofang; Epperly, Michael W.; Greenberger, Joel S.; Tang, Daolin

    2016-01-01

    Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs. FANCD2-deficient BMSCs were more sensitive to erastin-induced ferroptosis (but not autophagy) than FANCD2 wild-type cells. Knockout of FANCD2 increased ferroptosis-associated biochemical events (e.g., ferrous iron accumulation, glutathione depletion, and malondialdehyde production). Mechanically, FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). Collectively, these findings indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. FANCD2 could represent an amenable target for the development of novel anticancer therapies aiming to reduce the side effects of ferroptosis inducers.

  7. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  8. Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability.

    Science.gov (United States)

    Leiva, Magdalena; Quintana, Juan A; Ligos, José M; Hidalgo, Andrés

    2016-01-08

    The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFβ by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.

  9. MR imaging of normal bone marrow; Obraz MR prawidlowego szpiku kostnego

    Energy Technology Data Exchange (ETDEWEB)

    Stajgis, M.; Paprzycki, W. [Osrodek Diagnostyki Obrazowej IR, Akademia Medyczna, Poznan (Poland)

    1994-12-31

    Principles of MR bone marrow imaging on the basis of retrospective analysis of MR examinations of bone marrow in different anatomic sites in 200 patients have been discussed. Significance of different physiologic factors and processes such as age, steatosis, osteoporosis, conversion and reconversion, which influence on MR bone marrow images, have been emphasized. T1-weighted images obtained with spin-echo sequences give the most of information about bone marrow structure in MR. Thorough knowledge of bone marrow physiology and clinical status of the patient is indispensable in correct interpretation of hypointensive lesions on T1-weighted images. When presence of disseminated bone marrow disease is suspected, authors propose routine imaging of lumbar vertebral column, pelvis and proximal parts of femoral bones. (author) 7 refs, 7 figs

  10. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs.

    Science.gov (United States)

    Lee, Michelle H; Goralczyk, Anna G; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A; Toh, Sue-Anne; Yassin, M Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-02-17

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow.

  11. Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering.

    Science.gov (United States)

    Jung, Moonjung; Dunbar, Cynthia E; Winkler, Thomas

    2015-12-01

    The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patient-derived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.

  12. Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

    Science.gov (United States)

    Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

    2015-03-01

    To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Detection of lymphomatous infiltration in the bone marrow

    International Nuclear Information System (INIS)

    Cunha, M. O.; Santos, A. O.; Costa, S.C.; Ramos, C.D.; Etchebehere, E.C.S.C.; Metze, I.L.; Barbosa, M.N.S.; Souza, C.A.; Camargo, E.E.

    1997-01-01

    Full text: The scintillographic follow-up of patients with lymphoma is obtained by making whole body research (WBR) with gallium-67. However, the abnormal accumulation of this pharmaceutical in the long bones is not an specific for lymphomatous infiltration and can be representative of hematopoietic expansion of bone marrow, as well. The differential diagnosis can be done using bone scintillography (BS) and bone marrow scintillography (BMS). We present a case where the diagnosis of lymphomatous infiltration indicated by the WBR with gallium-67, was confirmed by the BS and BMS. Male patient, 57 years old, with diagnosis of a high level malignant non-Hodgkin lymphoma, was submitted to the WBR with gallium-67 during the chemotherapy. The gallium-67 was high uptaked in the third distal of the right femur and in the proximal of the right tibia. One month after finishing the chemotherapy, a new WBR with gallium-67 shows the persistence of the high uptake in the same areas and the appearance of new ones in the third distal of the left femur. The study was complemented with BS and BMS. The BS revealed high uptake in focal areas, in the same regions where high uptake of gallium-67 has been detected in the study, after chemotherapy. The BMS showed absence of functioning bone marrow in these areas reducing the probability of medullar expansion. The absence of answering to the chemotherapy has been verified, changing the patient behavior and prognostic. The BMS with colloidal Tc-99m sulfur in this patient was useful for the differential diagnosis between medullar expansion and lymphomatous medullar infiltration

  14. Protective effect of a non specific inflammation on bone marrow protein synthesis in irradiated mice

    International Nuclear Information System (INIS)

    Herodin, F.; Roques, P.; Court, L.

    1988-01-01

    Gamma radiations exert a decrease in mouse bone marrow total protein synthesis. A non-specific inflammatory process induced with polyacrylamide microbeads stimulates spleen and marrow protein synthesis and protects the medullar protein synthesis in irradiated mice [fr

  15. High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice.

    Science.gov (United States)

    Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas; Taipaleenmäki, Hanna; Nielsen, Tina Kamilla; Kassem, Moustapha

    2018-06-01

    Obesity represents a risk factor for development of insulin resistance and type 2 diabetes. In addition, it has been associated with increased adipocyte formation in the bone marrow (BM) along with increased risk for bone fragility fractures. However, little is known on the cellular mechanisms that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory genes (Tnfα, IL1β, Lcn2) and did not manifest an insulin resistant phenotype evidenced by normal levels of pAKT after insulin stimulation as well as normal levels of insulin signaling genes. In addition, BM progenitor cells manifested enhanced adipocyte differentiation in HFD condition. Thus, our data demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin resistance and inflammation in the BM suggest that BMAT buffers extra energy in the form of triglycerides and thus plays a role in whole-body energy homeostasis. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

  16. Usefulness of bone marrow magnetic resonance imaging and indium-111-chloride bone marrow scintigraphy in patients with various hematological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yutaka; Umekawa, Tsunekazu; Chikayama, Satoshi [Osaka General Hospital of West Japan Railway Compapy (Japan)] [and others

    1995-03-01

    This study investigated the ability of magnetic resonance (MR) imaging and indium-111 chloride (In-111) scintigraphy to assess bone marrow in various hematological lesions. The subjects were 7 with aplastic anemia (AA), 4 with myelodysplastic syndrome (MDS), 3 with polycythemia (PC), 3 with essential thrombocythemia (ET), 2 with multiple myeloma (MM), 2 with monoclonal gammopathy of undetermined significance (MGUS), 3 with idiopathic thrombocytopenic purpura (ITP), one with acute lymphocytic leukemia (ALL), and one with secondary anemia due to chronic inflammation (SA). Bone marrow cellularity was assessed on MR images and both uptake and tissue distribution were assessed on In-111 scintigraphy. Hypo-cellularity was seen in all AA patients, but not seen in any other patient in each group. On the other hand, hyper-cellularity was seen in 3 MDS, one PC, all 3 ET, one ALL, and one SA patients. In the group of MM, the vertebral body was seen as heterogenous signal intensity on MR images. Bone marrow was seen as iso-intensity in one MDS, 2 PC, all 2 MGUS, and all 3 ITP patients. In-111 scintigraphy showed decrease or disappearance of tracer uptake and decreased tissue distribution in all 7 AA, one MDS, one PC, and one ALL patients. Increased tracer uptake and enlarged tissue distribution were seen in one MDS, one PC, and one SA patients. One MDS, one ET, all 2 MM, all 2 MGUS, all 3 ITP patients had tracer uptake and tissue distribution that were equal to those in the normal tissues. Since MR imaging and In-111 scintigraphy provided qualitatively different information, the combination of both modalities would contribute to the understanding of bone marrow condition in hematopoietic diseases. (N.K.).

  17. Bone marrow adsorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts

    International Nuclear Information System (INIS)

    Klerk, J.M.H. de; Dieren, E.B. van; Schip, A.D. van het

    1996-01-01

    Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate ( 186 Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic method were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid E max model. The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm 50 (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for 186 Re-HEDP was on the order of 2 Gy. Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of 186 Re-HEDP. 33 refs., 1 fig., 1 tab

  18. The evaluation of the bone marrow accumulation of Ga-67 citrate

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi (Miyazaki Medical Coll., Kiyotake (Japan))

    1989-11-01

    The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author).

  19. The evaluation of the bone marrow accumulation of Ga-67 citrate

    International Nuclear Information System (INIS)

    Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi

    1989-01-01

    The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author)

  20. Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Pierpaoli, W.; Maestroni, G.J.M.

    1983-01-01

    Allogeneic, H-2-incompatible irradiation chimeras (H-2sup(d) → H-2sup(b)) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immuno-competent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease, and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism. (Auth.)

  1. Age-related distribution of vertebral bone-marrow diffusivity

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, Jochen, E-mail: j.herrmann@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Department of Pediatric Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Krstin, Nina, E-mail: ninakrstin@web.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Schoennagel, Bjoern P., E-mail: b.schoennagel@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Sornsakrin, Marjike, E-mail: m.sornsakrin@uke.de [Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg (Germany); Derlin, Thorsten, E-mail: t.derlin@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Busch, Jasmin D., E-mail: jd.busch@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Petersen, Kay Uwe, E-mail: Kay.Petersen@med.uni-tuebingen.de [Department of Psychiatry, University Clinic Tübingen, Calwerstraße 14 Tübingen 72076 (Germany); Graessner, Joachim, E-mail: joachim.graessner@siemens.com [Siemens AG Healthcare, Lindenplatz 2, 20099 Hamburg (Germany); Adam, Gerhard, E-mail: g.adam@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany); Habermann, Christian R., E-mail: c.habermann@uke.de [Department of Diagnostic and Interventional Radiology, Martinistraße 52, D-20246 Hamburg (Germany)

    2012-12-15

    Purpose: To determine age-related diffusivity changes of the lumbar bone marrow by measurement of apparent diffusion coefficient (ADC) values. Materials and methods: The local ethics committee approved this study and written informed consent was obtained. The study group comprised 88 individuals including 75 healthy volunteers and 13 patients (48 female, 40 male; mean age 36 years, range 0–84 years). The pediatric cases were recruited from patients. Echo-planar diffusion weighted imaging (DWI) was performed with b-values of 50, 400 and 800 s/mm{sup 2}. ADC-values were calculated and measured in the 1st and 2nd vertebral body of the lumbar spine. Correlation between age and ADC-values was analyzed with Spearman's rho test. Results: The ADC values of the vertebral bone marrow of the lumbar spine showed a significant negative correlation with age (rho = −0.398, p = 0.001). The mean ADC values (×10{sup −3} mm{sup 2}/s) in the age groups 0–29 years (mean age 18.0 years, n = 42) and 30–88 years (mean age 51.6 years, n = 46) were 0.54 ± 0.07 and 0.47 ± 0.08, respectively (p < 0.001, T-test). No significant differences were found between children and young adults. Conclusion: Bone marrow ADC values of the lumbar spine show a linear decrease with growing age and thereby reflect the gradual changes of cell composition occurring during marrow conversion.

  2. Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: Effect on bone marrow microenvironment.

    Directory of Open Access Journals (Sweden)

    Soraya Carrancio

    Full Text Available The aim of the present study was to determine how mesenchymal stem cells (MSC could improve bone marrow (BM stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34(+ progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin, involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (i.v. or intrabone (i.b. route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur.

  3. Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

    Science.gov (United States)

    Gil-Sanchis, Claudia; Cervelló, Irene; Khurana, Satish; Faus, Amparo; Verfaillie, Catherine; Simón, Carlos

    2015-06-01

    To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Prospective experimental animal study. University research laboratories. β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL(+) cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups. Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

    Science.gov (United States)

    Cho, H S; Oh, J H; Kim, H-S; Kang, H G; Lee, S H

    2007-02-01

    Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

  5. Utility of simultaneous assessment of bone marrow aspirates and trephine biopsy sections in various haematological disorders

    Directory of Open Access Journals (Sweden)

    Vandana Puri

    2018-01-01

    Conclusion: Bone marrow aspiration alone is sufficient for the diagnosis of megaloblastic anemia and most of the hematological malignancies. Bone marrow biopsy is more appropriate for detection of disorders with focal marrow involvement such as lymphoproliferative disorders, metastatic cancer, focal blast crisis in CML, granulomatous lesions, and hypoplastic marrow. However, it is strongly recommended that both should be reviewed simultaneously to ensure maximum diagnostic accuracy.

  6. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    Science.gov (United States)

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both pbones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

  7. Radiography and bone scintigraphy in bone marrow transplant multiple myeloma patients

    International Nuclear Information System (INIS)

    Aagren, B.; Aspelin, P.

    1997-01-01

    Purpose: To compare conventional radiography and bone scintigraphy in relation to clinical outcome in bone marrow transplant multiple myeloma patients. Material and Methods: A total of 70 radiographies and 70 bone scintigraphies were compared in 35 patients. Results: The skull, the extremities, the iliac and public bones were better assessed with radiography. For new vertebral lesions and for lesions in the ribs and sternum, bone scintigraphy proved superior. For the sacrum, the methods were equal. When bone scintigraphy was used as a complement to radiography, 4% more pathological sites were found. No patient had both a normal radiography and a pathological bone scintigraphy, but 5 patients had both a normal bone scintigraphy and a pathological radiography. The results of the radiological examinations did not always correlate with the clinician's grading of the patient's disease. The radiological examinations had no prognostic value for the 7 patients examined on several occasions. Conclusion: The ability of conventional radiography and bone scintigraphy to disclose myeloma lesions varies, depending on location and size of the lesions. Radiography should remain the primary examination modality also for bone marrow transplant multiple myeloma patients. Bone scintigraphy can severe as a complement for investigating unexplained pain, e.g. caused by lesions in vertebrae or ribs. (orig.)

  8. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  9. Bone marrow transplantation after the Chernobyl nuclear accident

    International Nuclear Information System (INIS)

    Baranov, A.; Gale, R.P.; Guskova, A.

    1989-01-01

    On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed

  10. Influence of bone marrow fat on the determination of bone mineral content by QCT

    International Nuclear Information System (INIS)

    Ikeda, Toshiaki; Sakurai, Kiyoko

    1994-01-01

    Single-energy quantitative CT (SEQCT) is thought to be suitable for long-term observation of changes in bone mineral content in individual patients. However, in patients with osteoporosis, an increase in bone marrow fat cannot be ignored. The relationship between bone marrow fat and bone mineral density (BMD) at different tube voltages of 80 kV and 120 kV was investigated using a set of solution phantoms that we devised, and was also studied in healthy volunteers. On the basis of the results obtained using the solution phantoms, the influence of bone marrow fat accounted for a decrease of 8.9 mg/cm 3 in BMD value at 80 kV and of 10.8 mg/cm 3 at 120 kV in the presence of 10 vol% fat. These findings suggested that the influence of fat was less at a lower tube voltage. The formulas used to estimate the true bone mineral and fat contents from the BMD values at low and high tube voltages were derived by eliminating the influence of beam hardening. Using these formulas, we studied healthy volunteers, and found that the difference between the true BMD value and the BMD value calibrated for beam hardening averaged 17.8 mg/cm 3 at 80 kV and 22.6 mg/cm 3 at 120 kV. Moreover, the estimated concentration of bone marrow fat in the volunteers averaged 25.0 vol%. In conclusion, because SEQCT performed at a low tube voltage is less influenced by bone marrow fat, it should be selected for assessment of the clinical response to therapy and for studying sequential changes. However, in patients with a low bone mineral content indicated by SEQCT, it would be worthwhile trying to estimate both true mineral and fat contents in bone using the formulas obtained in this study in order to differentiate decrease in bone mineral from interference by bone marrow fat. (author)

  11. The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1

    International Nuclear Information System (INIS)

    Scarantino, C.W.; Rubin, P.; Constine, L.S. III

    1984-01-01

    Bone marrow regeneration following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation to large volumes of bone marrow does not completely suppress bone marrow regeneration but results in a rapid compensatory response. Comparisons are made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow indicate significantly different response mechanisms. (Auth.)

  12. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

    Science.gov (United States)

    Rougraff, Bruce T; Kling, Thomas J

    2002-06-01

    The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

  13. Characteristic focal hot spots of bone marrow scintigraphic finding in aplastic anemia

    International Nuclear Information System (INIS)

    Liu Yong

    1991-01-01

    The bone marrow scintigraphy with 99m Tc sulfur colloid has been performed in 168 patients with Aplastic anemia(AA) and 100 patients with others hematological disorders. Bone marrow imaging is a useful method to demonstrate the existence of active hematopoietic foci in living body. The features and clinical significance of these focal hot spots have been discussed. The bone marrow scintigraphy is proved to be helpful in diagnosis, therapy and assessing prognosis of A.A

  14. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

    Directory of Open Access Journals (Sweden)

    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  15. Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

    International Nuclear Information System (INIS)

    Solomon, S.B.

    1980-06-01

    The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

  16. Positive indium-III bone marrow scan in metastatic breast carcinoma. Case report

    International Nuclear Information System (INIS)

    LaManna, M.M.; Hyzinski, M.; Swami, V.K.; Parker, J.A.

    1984-01-01

    Indium is generally presumed to localize in the bone marrow within the erythroid cell line. Fibrosis, inflammation, lymphoma, extended field radiation, chemotherapy, or combinations of both treatment modalities generally depress the uptake of indium by the marrow in a complex fashion. We report a case of metastatic breast carcinoma and pancytopenia in which the In-111 scan appeared qualitatively similar to a Tc-99m MDP bone scan. Findings were confirmed by bone marrow biopsy

  17. Analysis of glycoprotein E-selectin ligANDs on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells

    KAUST Repository

    Merzaban, Jasmeen; Burdick, Monica M.; Gadhoum, Samah; Dagia, Nilesh M.; Chu, Julia T.; Fuhlbrigge, Robert C.; Sackstein, Robert D.

    2011-01-01

    Although well recognized that expression of E-selectin on marrow microvessels mediates osteotropism of hematopoietic stem/progenitor cells (HSPCs), our knowledge regarding the cognate E-selectin ligand(s) on HSPCs is incomplete. Flow cytometry using

  18. Erythropoietic bone marrow in the pigeon: Development of its distribution and volume during growth and pneumatization of bones

    International Nuclear Information System (INIS)

    Schepelmann, K.

    1990-01-01

    During postnatal development of the pigeon, a large portion of the skeleton becomes pneumatized, displacing the hemopoietic bone marrow. The consequences of pneumatization on distribution and quantity of bone marrow as well as the availability of other sites for hemopoiesis have been investigated. Hemopoietic marrow of differently aged pigeons divided into five groups from 1 week posthatching (p.h.) up to 6 months p.h. was labeled with Fe-59 and examined by serial whole-body sections. Autoradiography and morphometry as well as scintillation counts of single bones and organs were also carried out. No sign of a reactivation of embryonic sites of erythropoiesis was found. Bone marrow weight and its proportion of whole-body weight increased during the first 4 weeks p.h. from 0.54% to 2.44% and decreased in the following months to about 1.0%. The developing bone marrow showed a progressive distribution during the first months of life, eventually being distributed proportionally over the entire skeleton, except for the skull. At the age of 6 months p.h. bone marrow had been displaced, its volume decreasing in correlation to increasing pneumaticity and conversion to fatty marrow. This generates the characteristic pattern of bone marrow distribution in adult pigeons, which shows hemopoietic bone marrow in ulna, radius, femur, tibiotarsus, scapula, furcula, and the caudal vertebrae

  19. Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture.

    Science.gov (United States)

    Lima, Florence; Swift, Joshua M; Greene, Elisabeth S; Allen, Matthew R; Cunningham, David A; Braby, Leslie A; Bloomfield, Susan A

    2017-10-01

    Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

  20. A comparison of treating Unicameral bone cyst using steroids and percutaneous autologous bone marrow aspiration injection.

    Science.gov (United States)

    Akram, Muhammad; Farooqi, Faheem Mubashir; Shahzad, Muhammad Latif; Awais, Syed Muhammad

    2015-11-01

    To compare the results of percutaneous autologous bone aspiration injection and steroids injections in the treatment of unicameral bone cyst. The prospective study was conducted at Mayo Hospital, Lahore, from January 2008 to March 2014, and comprised patients diagnosed radiologically as a case of unicameral bone cyst. The patients were divided into two groups, with group 1 being treated with bone marrow aspiration injection, while group 2 was given steroids injection. Aspiration of bone marrow was done from tibial tuberosity. The 30 patients in the study were divided into two groups of 15(50%) each. In group 1, 8(53.34%) patients and in group 2, 3 (20%) patients achieved healing after the first injection (p 0.05). The mean number of procedures required in group 1 was 1.57± 0.495 (range: 01-3) and for 2.19 ± 1.076 (range: 1-5) in group 2 (p 0.05). Bone marrow aspiration injection was better than steroids in treating unicameral bone cyst.

  1. [Effect of simvastatin on inducing endothelial progenitor cells homing and promoting bone defect repair].

    Science.gov (United States)

    Song, Quansheng; Wang, Lingying; Zhu, Jinglin; Han, Xiaoguang; Li, Xu; Yang, Yanlin; Sun, Yan; Song, Chunli

    2010-09-01

    To investigate the effect of simvastatin on inducing endothelial progenitor cells (EPCs) homing and promoting bone defect repair, and to explore the mechanism of local implanting simvastatin in promoting bone formation. Simvastatin (50 mg) compounded with polylactic acid (PLA, 200 mg) or only PLA (200 mg) was dissolved in acetone (1 mL) to prepare implanted materials (Simvastatin-PLA material, PLA material). EPCs were harvested from bone marrow of 2 male rabbits and cultured with M199; after identified by immunohistochemistry, the cell suspension of EPCs at the 3rd generation (2 x 10(6) cells/mL) was prepared and transplanted into 12 female rabbits through auricular veins (2 mL). After 3 days, the models of cranial defect with 15 cm diameter were made in the 12 female rabbits. And the defects were repaired with Simvastatin-PLA materials (experimental group, n=6) and PLA materials (control group, n=6), respectively. The bone repair was observed after 8 weeks of operation by gross appearance, X-ray film, and histology; gelatin-ink perfusion and HE staining were used to show the new vessels formation in the defect. Fluorescence in situ hybridization (FISH) was performed to show the EPCs homing at the defect site. All experimental animals of 2 groups survived to the end of the experiment. After 8 weeks in experimental group, new bone formation was observed in the bone defect by gross and histology, and an irregular, hyperdense shadow by X-ray film; no similar changes were observed in control group. FISH showed that the male EPC containing Y chromosome was found in the wall of new vessels in the defect of experimental group, while no male EPC containing Y chromosome was found in control group. The percentage of new bone formation in defect area was 91.63% +/- 4.07% in experimental group and 59.45% +/- 5.43% in control group, showing significant difference (P < 0.05). Simvastatin can promote bone defect repair, and its mechanism is probably associated with inducing EPCs

  2. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Auregan Gwenaelle

    2008-06-01

    Full Text Available Abstract Background Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. Results The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%. A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.

  3. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  4. Megakaryocytopoiesis and the number of thrombocytes after bone marrow cell transplantation in lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Hermanova, E.; Zoubkova, M.

    1977-01-01

    Changes were studied in the number of thrombocytes in the peripheral blood and megakaryocytes in the bone marrow and spleen in lethally irradiated mice after the transplantation of bone marrow cells. It was found that the thrombocytes increased in dependence on time after transplantation with the maximal values around the 20th day. An increased megakaryocytopoiesis was observed not only in the bone marrow but also in the spleen. These ascertainments suggest the importance of the transplantation of bone marrow cells and the role of thrombocytes for the survival of the organism after irradiation. (author)

  5. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    International Nuclear Information System (INIS)

    Lawton, C.A.; Fish, B.L.; Moulder, J.E.

    1994-01-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs

  6. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

    International Nuclear Information System (INIS)

    Ambrus, C.M.; Ambrus, J.L.

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

  7. Osteonecrosis of the femoral head after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi; Jun, Jeong Su; Park, Chang Suk; Kim, Yong Sik; Kwon, Soon Yong; Kim, Yoo Jin; Kim, Chun Choo [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2003-07-01

    To retrospectively review findings of osteonecrosis of the femoral head after bone marrow transplantation. We reviewed the clinical and MR findings of osteonecrosis of the femoral head in 23 of 1112 patients who underwent marrow transplantation during a five-year follow-up period lasting from 1996 to 2000. Mean age at the time of diagnosis was 31 (range, 20-47) years, and the mean time from transplant to diagnosis was 17 months. All patients developed variable graft-versus-host disease and seventeen were treated with high-dose prednisolone and/or cysclosporin for severe acute or extensive chronic graft versus host disease. Osteonecrosis was diagnosed by magnetic resonance (MR) imaging, which allowed early detection of disease assessment of its stage. At the time of diagnosis, 15 hips were at stage I, 28 at stage II, two at stage III, and none at stage IV, according to the international ARCO classification system. Osteonecrosis of femoral diaphyses, the lower lumbar spine, or pelvic bones in the MR field was also found to have occurred in 11 patients. Initial treatment was conservative: 21 hips underwent surgery [core decompression (n=10), vascularized fibular bone graft (n=5), and joint replacement (n=6)]. In patients receiving high-dose steroids for the treatment of graft-versus-host disease, MR screening might help detect osteonecrosis at an early stage.

  8. Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

    Science.gov (United States)

    Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

    2017-07-01

    The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

  9. Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

    International Nuclear Information System (INIS)

    Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C.; Thomsen, Felix; Campbell, Graeme M.

    2016-01-01

    Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm 3 corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive

  10. Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C., E-mail: glueer@rad.uni-kiel.de [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118 (Germany); Thomsen, Felix [Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Sur, Bahía Blanca 8000 (Argentina); Campbell, Graeme M. [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118, Germany and Institut für Biomechanik, Technische Universität Hamburg-Harburg (TUHH), Hamburg 21073 (Germany)

    2016-07-15

    Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm{sup 3} corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive

  11. Antibody formation in mouse bone marrow. IV. The influence of splenectomy on the bone marrow plaque-forming cell response to sheep red blood cells

    International Nuclear Information System (INIS)

    Benner, R.; Oudenaren, A. van

    1975-01-01

    Mouse bone marrow is barely capable of plaque-forming cell (PFC) activity during the primary response to sheep red blood cells (SRBC). However, during the secondary response, it becomes the major center of activity containing IgM-, IgG- and IgA-PFC. In the present paper the influence of splenectomy was studied on primary and secondary PFC activity in the bone marrow. Differences in primary and secondary bone marrow PFC responses are probably related to the presence of B and T memory cells in situ. Therefore the effect of splenectomy on the appearance of B and T memory cells in the bone marrow was also investigated. iv.plenectomy before intravenous (iv) immunization with 4 x 10 8 SRBC prevented any primary PFC activity in the bone marrow. The influence of splenectomy before priming on secondary PFC activity in the bone marrow depended on the priming dose of SRBC. Splenectomy before priming with 10 7 SRBC iv completely prevented IgM-, IgG-, and IgA-PFC activity in the bone marrow upon subsequent boosting with 4 x 10 8 SRBC iv. By means of cell transfer experiments it was shown that after splenectomy no B or T memory cells appeared in the bone marrow after priming with 10 7 SRBC iv. Cell transfer experiments showed that splenectomy before priming with 10 7 SRBC iv not only interfered with the appearance of B and T memory cells in the bone marrow, but also with the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood. Immunization of spenectomized mice with 4 x 10 8 SRBC iv induced the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood

  12. Neurospheres induced from bone marrow stromal cells are multipotent for differentiation into neuron, astrocyte, and oligodendrocyte phenotypes

    International Nuclear Information System (INIS)

    Suzuki, Hidenori; Taguchi, Toshihiko; Tanaka, Hiroshi; Kataoka, Hideo; Li Zhenglin; Muramatsu, Keiichi; Gondo, Toshikazu; Kawai, Shinya

    2004-01-01

    Bone marrow stromal cells (MSCs) can be expanded rapidly in vitro and have the potential to be differentiated into neuronal, glial and endodermal cell types. However, induction for differentiation does not always have stable result. We present a new method for efficient induction and acquisition of neural progenitors, neuronal- and glial-like cells from MSCs. We demonstrate that rat MSCs can be induced to neurospheres and most cells are positive for nestin, which is an early marker of neuronal progenitors. In addition, we had success in proliferation of these neurospheres with undifferentiated characteristics and finally we could obtain large numbers of neuronal and glial phenotypes. Many of the cells expressed β-tubulin III when they were cultivated with our method. MSCs can become a valuable cell source as an autograft for clinical application involving regeneration of the central nervous system

  13. Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute

    International Nuclear Information System (INIS)

    Elgamal, B.M.; Rashed, R.A.; Raslan, H.N.

    2011-01-01

    Bone marrow necrosis; Egyptian cancer patients Abstract Background: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. Methods: study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). Results: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. Conclusion: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome

  14. Pulmonary complications after bone marrow transplantation in chest radiography

    Energy Technology Data Exchange (ETDEWEB)

    Schuster, J.; Sailer, M.; Schmeiser, T.; Schumacher, K.A.; Heit, W.

    1988-01-01

    In a retrospective study chest radiographs of 87 bone marrow transplant recipients were analysed. 36 patients had pulmonary complications with lung opacifications. Interstitial changes were more frequent than air-space pneumonias. The latter were caused by bacteria and fungi only. The most common cause of pulmonary complications was cytomegalovirus pneumonia. It was characterised uniformly by a bilateral diffuse interstitial pattern. Idiopathic interstitial pneumonias were indistinguishable from CMV infection. Pneumonias caused by Epstein-Barr virus and protozoa, diffuse radiation pneumonitis and leukaemic infiltrates were rare and also associated with interstitial changes.

  15. Pulmonary complications after bone marrow transplantation in chest radiography

    International Nuclear Information System (INIS)

    Schuster, J.; Sailer, M.; Schmeiser, T.; Schumacher, K.A.; Heit, W.; Ulm Univ.

    1988-01-01

    In a retrospective study chest radiographs of 87 bone marrow transplant recipients were analysed. 36 patients had pulmonary complications with lung opacifications. Interstitial changes were more frequent than air-space pneumonias. The latter were caused by bacteria and fungi only. The most common cause of pulmonary complications was cytomegalovirus pneumonia. It was characterised uniformly by a bilateral diffuse interstitial pattern. Idiopathic interstitial pneumonias were indistinguishable from CMV infection. Pneumonias caused by Epstein-Barr virus and protozoa, diffuse radiation pneumonitis and leukaemic infiltrates were rare and also associated with interstitial changes. (orig.) [de

  16. Chromosome abnormalities in bone marrow of Thorotrast administered patients

    International Nuclear Information System (INIS)

    Ishihara, T.; Minamihisamatsu, M.

    1987-01-01

    The chromosomally abnormal clones occurring with high frequencies in bone marrow of 3 Thorotrast administered patients were studied by annual follow up observations. In one case the frequency of the clone was maintained fairly constant, but in another case it showed a tendency of increase, and in still another case the frequency of the clone showed drastic changes from year to year. The karyotypes of the clones showed remarkable chromosome abnormalities, among which the large partial loss of chromosomes was especially noted in all the 3 cases. (author)

  17. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.

    2015-01-01

    Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...... and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis....

  18. Bone marrow amyloid spherulites in a case of AL amyloidosis.

    Science.gov (United States)

    Bommannan B K, Karthik; Sonai, Mukinkumar; Sachdeva, Man Updesh Singh

    2016-05-01

    Parallel arrangement of β-pleated sheets by amyloidogenic proteins is a well known phenomenon. Rarely, amyloid fibrils undergo radial orientation to form globular structures called spherulites. These amyloid spherulites show Maltese cross pattern under polarized microscopy. The clinical significance of amyloid spherulites is undetermined. Amyloidogenic proteins like insulin and β-lactoglobulin form spherulites in vitro. The senile plaques of Alzheimer's disease rarely form in vivo spherulites. Amyloid spherulites have been described in the liver and small intestine. For the first time, we document amyloid spherulite formation in the bone marrow biopsy of an AL amyloidosis patient. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effect of 241-americium on bone marrow stroma

    International Nuclear Information System (INIS)

    Heuvel, R. van den

    1990-01-01

    The regulation of haemopoiesis occurs via complex interactions between the stroma and the haemopoietic cells. An attempt to further clarifying the mechanisms and the exact role of the stroma in the regulation was made in a study. Results revealed that the murine bone marrow stromal cells are highly radiosensitive after injection with 241-americium and can thus be considered as a target population after internal contamination. In addition, observations are made which may be important for risk estimation for the developing animal and during pregnancy. Contamination in utero and by lactation shows persistent damage up to 1 year after contamination at an average annual dose of 5 cGy. (author)

  20. The clinical experience of radiocolloid bone marrow scintigraphy

    International Nuclear Information System (INIS)

    Kanaev, S.V.; Novikov, S.N.; Zhukova, L.A.

    1997-01-01

    Results of the bone marrow (BM) scintigraphy in 129 patients with various malignant neoplasms and 10 practically healthy persons are discussed. Domestic preparations Technefit and Koren labelled with 99m Tc and injected intravenously were used as radiopharmaceuticals. Apex-SP6 gamma camers (Eliscint company, Israel) was applied. The possibility of obtaining BM qualitative pattern permitting to perform the efficient diagnosis o BM metastases in oncological patients is shown. Dependence between the expansion of colloid radiopharmaceuticals concentration area (hemopoiesis peripheric expansion rate) and the BM metastases availability was not confirmed

  1. Bone marrow-derived CD13+ cells sustain tumor progression

    Science.gov (United States)

    Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2014-01-01

    Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b+CD13+ myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b+CD13+ myeloid cells could become a non-malignant target for the development of novel anticancer regimens. PMID:25339996

  2. Development of a 3D bone marrow adipose tissue model.

    Science.gov (United States)

    Fairfield, Heather; Falank, Carolyne; Farrell, Mariah; Vary, Calvin; Boucher, Joshua M; Driscoll, Heather; Liaw, Lucy; Rosen, Clifford J; Reagan, Michaela R

    2018-01-26

    Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic

  3. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

    Directory of Open Access Journals (Sweden)

    Mary C. Farach-Carson

    2017-08-01

    Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

  4. Bone marrow transplantation in miniature swine: I. Autologous and SLA matched allografts

    International Nuclear Information System (INIS)

    Pennington, L.R.; Pescovitz, M.D.; Popitz, F.; Sachs, D.H.; Sakamoto, K.

    1986-01-01

    We developed a successful bone marrow transplant protocol in MHC-inbred miniature swine (MS). Three groups of MS were studied: irradiation controls, autologous bone marrow transplants and SLA matched bone marrow allografts. One day prior to irradiation, all animals underwent Hickman catheter placement via the external jugular vein. Bone marrow was harvested by direct mechanical removal of marrow from four long bones in Groups 2 and 3 one day prior to irradiation. All animals received 900 rads of midline body radiation from a Cobalt-60 source, were treated 1 g of cephalothin IV bid from day 1 to 14, 20 mg of genetamicin IV bid, from day 4 through 14 and 250 to 350 ml of fresh, irradiated whole blood from blood group identical donors on days 7, 11 and 14. Bone marrow was filtered, washed, stored overnight at 4 C and reinfused one to six hr after irradiation. Engraftment was defined by return of the peripheral WBC to 1000/mm 3 . All six animals in Group 1 died of aplasia between days 7 and 12. Marrow engrafted in eight of 12 animals in Group 2 and 7 of 10 animals in Group 3. This model provides a means to study the biological characteristics of bone marrow transplantation in immunologically well characterized large animals and should prove useful as a model for bone marrow transplants in man

  5. Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

    Science.gov (United States)

    Datta, N K; Das, K P; Alam, M S; Kaiser, M S

    2014-07-01

    Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is unicameral bone cyst.

  6. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  7. Parental bone marrow growth in young hybrid mice

    International Nuclear Information System (INIS)

    Chervenak, R.P.

    1979-01-01

    When bone marrow is transplated from certain inbred mouse strains to F 1 hybrids of that strain, the graft often fails to proliferate. It has been reported that this phenomenon, known as Poor Growth, is not demonstrable in recipients less than three weeks of age. The purpose of the present study was to investigate some of the parameters involved in this phenomenon and its sudden appearance at three weeks of age. By employing 125 IUdR uptake and hemopoietic colony assays following transplantation of marrow to mice of various ages and treatment groups, the following conclusions were drawn. (1) Parental marrow grew equally well in both parental strain and F 1 hybrid recipients less than three weeks old; (2) The observed growth of hemopoietic tissue was not due to endogeneous stem cell proliferation; (3) Changes in radiation sensitivity did not account for the fluctuations of hemopoiesis seen in mice from one to five weeks of age; (4) Neither stimulator cells in mice less than three weeks of age nor graft destroying cells in older mice could be demonstrated. Two mechanistic models of Poor Growth are presented and discussed and a new model is proposed

  8. Bone marrow transplantation for patients with chronic myeloid leukemia

    International Nuclear Information System (INIS)

    Goldman, J.M.; Apperley, J.F.; Jones, L.

    1986-01-01

    Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72%, and the actuarial risk of relapse was 7%. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18%, and the actuarial risk of relapse was 42%. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established

  9. Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

    Science.gov (United States)

    Suchacki, Karla J; Cawthorn, William P

    2018-01-01

    The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

  10. [Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

    Science.gov (United States)

    Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

    2017-01-01

    Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then o