WorldWideScience

Sample records for bone marrow progenitor

  1. Transplantable NK cell progenitors in murine bone marrow.

    Science.gov (United States)

    Moore, T; Bennett, M; Kumar, V

    1995-02-15

    Differentiation of NK cells from pluripotent hematopoietic stem cells is a poorly understood process. Although it is known that NK cells are bone marrow derived and dependent upon an intact bone marrow microenvironment for complete maturation, it is not known if they arise from an intermediate lymphoid stem cell or from progenitors exclusively committed to the NK lineage. To determine whether phenotypically distinct committed NK progenitor cells exist in murine bone marrow, we sorted cells capable of repopulating recipient mice with mature NK cells upon i.v. transfer. We identified a rare population of bone marrow cells with the phenotype Ly6+ Lin- c-kit+ CD43high Fall-3high TSA-1- AA4.1low Rh123high that is highly enriched for the ability to generate NK cells after transplantation. Although these cells are relatively depleted of Rh123low pluripotent stem cells, they are highly enriched for both lymphoid and myeloid repopulating ability. Thus, we have found no evidence to support the existence of a phenotypically distinct transplantable progenitor population in mouse bone marrow that is either exclusively committed to the NK cell lineage or exhibits the functional characteristics of a common lymphoid stem cell.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. 

  5. Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Muellbacher, A.; Hume, D.; Braithwaite, A.W.; Waring, P.; Eichner, R.D.

    1987-06-01

    The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras.

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

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

  7. Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

    Science.gov (United States)

    Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:23555959

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation.

    Science.gov (United States)

    Hilton, Matthew J; Tu, Xiaolin; Wu, Ximei; Bai, Shuting; Zhao, Haibo; Kobayashi, Tatsuya; Kronenberg, Henry M; Teitelbaum, Steven L; Ross, F Patrick; Kopan, Raphael; Long, Fanxin

    2008-03-01

    Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms controlling their fate decisions. To investigate the potential role of Notch signaling in osteoblastogenesis, we used conditional alleles to genetically remove components of the Notch signaling system during skeletal development. We found that disruption of Notch signaling in the limb skeletogenic mesenchyme markedly increased trabecular bone mass in adolescent mice. Notably, mesenchymal progenitors were undetectable in the bone marrow of mice with high bone mass. As a result, these mice developed severe osteopenia as they aged. Moreover, Notch signaling seemed to inhibit osteoblast differentiation through Hes or Hey proteins, which diminished Runx2 transcriptional activity via physical interaction. These results support a model wherein Notch signaling in bone marrow normally acts to maintain a pool of mesenchymal progenitors by suppressing osteoblast differentiation. Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway.

  10. Bone marrow-derived progenitor cells augment venous remodeling in a mouse dorsal skinfold chamber model.

    Directory of Open Access Journals (Sweden)

    Megan E Doyle

    Full Text Available The delivery of bone marrow-derived cells (BMDCs has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM and Lin(-/Sca-1(+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1(+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1(+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif ligand 2 (CXCL2 and interferon gamma (IFNγ that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, and platelet derived growth factor-BB (PDGF-BB compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45(+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1(+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment.

  11. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    Directory of Open Access Journals (Sweden)

    Yaling Liu

    Full Text Available We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  12. Osterix-Cre Labeled Progenitor Cells Contribute to the Formation and Maintenance of the Bone Marrow Stroma

    Science.gov (United States)

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S.; Wang, Wen; Rowe, David W.; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma. PMID:23951132

  13. Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation.

    Science.gov (United States)

    Mizrahi, K; Stein, J; Pearl-Yafe, M; Kaplan, O; Yaniv, I; Askenasy, N

    2010-07-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway has selective toxicity to malignant cells. The TRAIL receptors DR4 and DR5 are expressed at low levels in human umbilical cord blood cells (3-15%) and are upregulated by incubation with the cognate ligand, triggering apoptosis in 70-80% of receptor-positive cells (P<0.001). Apoptosis is not induced in hematopoietic progenitors, as determined from sustained severe combined immunodeficiency reconstituting potential and clonogenic activity. Furthermore, elimination of dead cells after incubation with TRAIL for 72 h results in a threefold enrichment in myeloid progenitors. Exposure to TRAIL in semisolid cultures showed synergistic activity of DR4 and granulocyte/macrophage colony-stimulating factor in recruiting lineage-negative (lin(-)) and CD34(+) progenitors and in promoting the formation of large colonies. In murine bone marrow, approximately 30% of lin(-) cells express TRAIL-R2 (the only murine receptor), and the receptor is upregulated after transplantation in cycling and differentiating donor cells that home to the host marrow. However, this receptor is almost ubiquitously expressed in the most primitive (lin(-)SCA-1(+)c-kit(+)) progenitors, and stimulates the clonogenic activity of lin(-) cells (P<0.001), suggesting a tropic function after transplantation. It is concluded that TRAIL does not trigger apoptosis in hematopoietic progenitors, and upregulation of its cognate receptors under stress conditions mediates tropic signaling that supports recovery from hypoplasia.

  14. Bone marrow aspiration

    Science.gov (United States)

    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. Ex vivo expansions and transplantations of mouse bone marrow-derived hematopoietic stem/progenitor cells

    Institute of Scientific and Technical Information of China (English)

    WANG Jin-fu(王金福); WU Yi-fan(吴亦凡); HARRINTONG Jenny; McNIECE Ian K.

    2004-01-01

    To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells,CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded cells by the co-culture with MSCs may result in more rapid engraftment ofneutrophils following infusion to transplant recipients.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Beyth, Shaul; Mosheiff, Rami; Safran, Ori; Daskal, Anat; Liebergall, Meir

    2015-01-01

    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. PMID:26346476

  18. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors.

    Science.gov (United States)

    Muschler, G F; Nitto, H; Boehm, C A; Easley, K A

    2001-01-01

    Bone marrow harvested by aspiration contains connective tissue progenitor cells which can be induced to express a bone phenotype in vitro. The number of osteoblastic progenitors can be estimated by counting the colony-forming units which express alkaline phosphatase (CFU-APs). This study was undertaken to test the hypothesis that human aging is associated with a significant change in the number or prevalence of osteoblastic progenitors in the bone marrow. Four 2-ml bone marrow aspirates were harvested bilaterally from the anterior iliac crest of 57 patients, 31 men (age 15-83) and 26 women (age 13-79). A mean of 64 million nucleated cells was harvested per aspirate. The mean prevalence of CFU-APs was found to be 55 per million nucleated cells. These data revealed a significant age-related decline in the number of nucleated cells harvested per aspirate for both men and women (P = 0.002). The number of CFU-APs harvested per aspirate also decreased significantly with age for women (P = 0.02), but not for men (P = 0.3). These findings are relevant to the harvest of bone marrow derived connective tissue progenitors for bone grafting and other tissue engineering applications, and may also be relevant to the pathophysiology of age-related bone loss and post-menopausal osteoporosis.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    Science.gov (United States)

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  1. Mast Cell-activated Bone Marrow Mesenchymal Stromal Cells Regulate Proliferation and Lineage Commitment of CD34+ Progenitor cells

    Directory of Open Access Journals (Sweden)

    Zoulfia eAllakhverdi

    2013-12-01

    Full Text Available Background: Shortly after allergen exposure, the number of bone marrow and circulating CD34+ progenitors increases. We aim to analyze the possible mechanism whereby the allergic reaction stimulates bone marrow to release these effector cells in increased numbers. We hypothesize that mast cells may play a predominant role in this process. Objective: To examine the effect of IgE-activated mast cells on bone marrow mesenchymal stromal cells which regulate proliferation and differentiation of CD34+ progenitors. Methods: Primary mast cells were derived from CD34+ precursors and activated with IgE/anti-IgE. Bone marrow mesenchymal stromal cells were co-cultured with CD34+ progenitor cells and stimulated with IL1/TNF or IgE/anti-IgE activated mast cells in Transwell system. Results: Bone marrow mesenchymal stromal cells produce low level of TSLP under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines IL-1 and TNF or IgE-activated mast cells. The latter also triggers BM-MSCs production of G-CSF, and GM-CSF while inhibiting SDF-1. Mast cell-activated mesenchymal stromal cells stimulate CD34+ cells to proliferate and to regulate their expression of early allergy-associated genes. Conclusion and Clinical Relevance: This in vitro study indicates that IgE-activated mast cells trigger bone marrow mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34+ precursor cells. The data predict that the effective inhibition of mast cells should impair mobilization and accumulation of allergic effector cells and thereby reduce the severity of allergic diseases.

  2. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats.

    Science.gov (United States)

    Lobach, Alexandra R; Uetrecht, Jack

    2014-07-21

    Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF). Employing a rat model of clozapine treatment, we set out to determine if the neutrophilia observed at the start of treatment is characteristic of G-CSF-associated bone marrow stimulation. Female Sprague-Dawley rats were treated with 30 mg/kg/day of clozapine for 10 days, and sustained neutrophilia was evident after 1 week of treatment paired with spikes in G-CSF. Within the bone marrow, clozapine was found to induce proliferation of the granulocyte progenitor colonies as measured by a methylcellulose assay. This led to elevated granulopoiesis observed by H&E and myeloperoxidase staining of bone marrow slices. Increased release of neutrophils from the marrow to the circulation was measured through 5-bromo-2'-deoxyuridine labeling in vivo, and these neutrophils appeared to be less mature based on (a) a decrease in the nuclear lobe count and (b) increased expression of surface CD62L. Furthermore, faster transit of the neutrophils through the marrow was suggested by a shift toward elevated numbers of neutrophils in the bone marrow maturation pool and increased CD11b and CD18 staining on the less mature neutrophils residing in the marrow. Taken together, these data indicate that clozapine stimulates the bone marrow to produce more neutrophils in a manner that is characteristic of endogenous G-CSF stimulation, and it is consistent with the inflammatory response observed in patients treated with clozapine.

  3. Effects of Astragalus polysaccharide on bone marrow and spleen progenitor cells in mitomycin—induced myelosuppresive mice

    Institute of Scientific and Technical Information of China (English)

    XiaX; CuiYJ

    2002-01-01

    Astragalus polysaccharide(APS) is an extract of Astragalus membranaceus Var.mongolicus.The effects of APS on bone marrow and spleen progenitor cells in mitomycin (MMS)-induced myelosuppressive micr was observed.MMC7 mg·kg-1 was injected ip on day 0,APS 100mg·kg-1·d-1 was given ac in 3 reginens (1)on day 0-4,(2)on day 0-11,(3)12 doses in 3 weeks.APS increased the number of bone marrow progeniter cells(CFU-C) of MMC treated micr 3-fold,from 1870±40 per femur to 6240±110 per femur on day3.APS treatment resulted in a higher level of bone marrow CFU-C at all time points from day 3 to day 18,in comparison with the control group.APS also significantly stimulated the proliferation of spleen pregenitor cells on day 14 (3-fold higher) and day 18(4-fold higher) after MMC treatment,although APS had no effect on spleen progenitor cells before day 14.These results demonstrate that APS enhances the proliferation and maturation of the progenitors of peripheral blood cells in MMC treated mice.

  4. Bone marrow transplant

    Science.gov (United States)

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Differentiation of Murine Bone Marrow-Derived Smooth Muscle Progenitor Cells Is Regulated by PDGF-BB and Collagen.

    Directory of Open Access Journals (Sweden)

    Clifford Lin

    Full Text Available Smooth muscle cells (SMCs are key regulators of vascular disease and circulating smooth muscle progenitor cells may play important roles in vascular repair or remodelling. We developed enhanced protocols to derive smooth muscle progenitors from murine bone marrow and tested whether factors that are increased in atherosclerotic plaques, namely platelet-derived growth factor-BB (PDGF-BB and monomeric collagen, can influence the smooth muscle specific differentiation, proliferation, and survival of mouse bone marrow-derived progenitor cells. During a 21 day period of culture, bone marrow cells underwent a marked increase in expression of the SMC markers α-SMA (1.93 ± 0.15 vs. 0.0008 ± 0.0003 (ng/ng GAPDH at 0 d, SM22-α (1.50 ± 0.27 vs. 0.005 ± 0.001 (ng/ng GAPDH at 0 d and SM-MHC (0.017 ± 0.004 vs. 0.001 ± 0.001 (ng/ng GAPDH at 0 d. Bromodeoxyuridine (BrdU incorporation experiments showed that in early culture, the smooth muscle progenitor subpopulation could be identified by high proliferative rates prior to the expression of smooth muscle specific markers. Culture of fresh bone marrow or smooth muscle progenitor cells with PDGF-BB suppressed the expression of α-SMA and SM22-α, in a rapidly reversible manner requiring PDGF receptor kinase activity. Progenitors cultured on polymerized collagen gels demonstrated expression of SMC markers, rates of proliferation and apoptosis similar to that of cells on tissue culture plastic; in contrast, cells grown on monomeric collagen gels displayed lower SMC marker expression, lower growth rates (319 ± 36 vs. 635 ± 97 cells/mm2, and increased apoptosis (5.3 ± 1.6% vs. 1.0 ± 0.5% (Annexin 5 staining. Our data shows that the differentiation and survival of smooth muscle progenitors are critically affected by PDGF-BB and as well as the substrate collagen structure.

  7. Flow cytometric immunophenotyping of feline bone marrow cells and haematopoietic progenitor cells using anti-human antibodies.

    Science.gov (United States)

    Araghi, Atefeh; Nassiri, Seyed Mahdi; Atyabi, Nahid; Rahbarghazi, Reza; Mohammadi, Elham

    2014-04-01

    There is a paucity of species-specific antibodies available for feline haematopoietic conditions. The purpose of this study was to broaden the panel of antibodies available for use in the immunophenotypic characterisation of feline haematopoietic cells by testing clones of anti-human monoclonal antibodies (mAbs) on normal, neoplastic and cultured feline haematopoietic progenitors to determine cross-reactivity to feline counterparts. In this study, 24 clones of anti-human mAbs were tested on normal or neoplastic feline bone marrow and peripheral blood cells. Six of these mAbs, including anti-cluster of differentiation (CD)61, anti-CD18, anti-CD14, anti-CD235a, anti-CD41 and anti-CD29, cross-reacted with normal feline bone marrow cells, whereas anti-CD33 and anti-CD117 cross-reacted with the blast cells in the bone marrow of two cats with myelodysplastic syndrome, and anti-CD71, anti-235a, anti-41 and anti-42 cross-reacted with immature erythroid cells in a cat with erythroleukaemia. In a feline immunodeficiency virus-positive cat, bone marrow cells were labelled with anti-CD33, anti-14 and anti-45. Anti-CD18, anti-CD14, anti-CD41 and anti-CD61 also reacted with the peripheral blood cells of the healthy cats. The feline haematopoietic progenitors formed colonies in the methylcellulose-based semisolid medium with significant enrichment of colony-forming unit-granulocyte, monocyte and burst-forming unit-erythroid. A panel of six anti-feline mAbs (anti-CD21-like, anti-T lymphocytes, anti-CD172a, anti-granulocyte, anti-CD45-like and anti-CD18) and eight anti-human antibodies (anti-CD71, anti-CD33, anti-CD235a, anti-CD41, anti-CD61, anti-CD117, anti-CD38 and anti-CD34) were used for the immunophenotypic characterisation of the feline bone marrow progenitors. CD45, CD33, CD235a and CD18 were expressed by the feline haematopoietic progenitor cells, with the highest expression level for CD45.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Impaired function of bone marrow-derived endothelial progenitor cells in murine liver fibrosis.

    Science.gov (United States)

    Shirakura, Katsuya; Masuda, Haruchika; Kwon, Sang-Mo; Obi, Syotaro; Ito, Rie; Shizuno, Tomoko; Kurihara, Yusuke; Mine, Tetsuya; Asahara, Takayuki

    2011-01-01

    Liver fibrosis (LF) caused by chronic liver damage has been considered as an irreversible disease. As alternative therapy for liver transplantation, there are high expectations for regenerative medicine of the liver. Bone marrow (BM)- or peripheral blood-derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat liver cirrhosis. We investigated the biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were subcutaneously injected with carbon tetrachloride (CCl(4)) every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical examination. Assessments of EPC in the peripheral blood and BM were performed by flow cytometry and EPC colony-forming assay, respectively, using purified MNCs and BM c-KIT(+), Sca-1(+), and Lin(-) (KSL) cells. Liver tissues underwent histological analysis with hematoxylin/eosin/Azan staining, and spleens were excised and weighed. CCl(4)-treated mice exhibited histologically bridging fibrosis, pseudolobular formation, and splenomegaly, indicating successful induction of LF. The frequency of definitive EPC-colony-forming-units (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells decreased significantly (p changes in primitive EPC-CFU occurred in LF mice. The frequency of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF mice compared with control mice. Together, these findings indicated the existence of impaired EPC function and differentiation in BM-derived EPCs in LF mice and might be related to clinical LF.

  10. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    Institute of Scientific and Technical Information of China (English)

    Donnahue; Dennie; Jean-Pierre; Louboutin; David; S; Strayer

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors

  11. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    Science.gov (United States)

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Induction of corneal epithelial progenitors from bone-marrow mesenchymal stem cells of rhesus monkeys in vitro

    Institute of Scientific and Technical Information of China (English)

    YUAN Jing; YU JianXiong; HUANG Bing; LIU BingQian; LIU JingBo; JIANG RuZhang; GE Jian

    2007-01-01

    Bioengineered corneas are substitutes for human donor tissue that are designed to treat severe disease affecting ocular surfaces.However, a shortage of candidate seed cells for bioengineering corneas is still a problem.Bone-marrow mesenchymal stem cells (MSCs) are capable of multilineage differentiation.Therefore, we determined whether MSCs differentiate into corneal epithelial cells (ECs).We applied three exoteric-microenvironmental systems to induce MSCs to become ECs.Induced MSC were identified by means of morphologic examination, immunocytochemical analysis, and flow cytometry.MSCs grown in one microenvironment had characteristics similar to those of corneal epithelial progenitors.Induced MSCs expressed markers for EC, including integrin β1, Cx43, Pax6, and P63.MSCs were successfully induced to become corneal epithelial progenitors.Therefore, the use of MSCs may hold substantial promise for reconstructing the ocular surface after corneal injury.

  14. Effects of bone marrow-derived endothelial progenitor cell transplantation on vein microenvironment in a rat model of chronic thrombosis

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-qiang; MENG Qing-you; WU Hao-rong

    2007-01-01

    Background Endothelial progenitor cells(EPCs) have been used in both experimental studies and clinical treatments of limb ischemia,as well as in the construction of engineered vascular tissue.The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis.Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation,cultured,and then transplanted into experimentally induced thrombi into inferior vena cava through the femoral vein.Vascular endothelial growth factor(VEGF),angiopoietin-1(ANG-1) and monocyte chemotactic protein-1(MCP-1) mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation.Results Levels of VEGF,ANG-1,and MCP-1 mRNA in EPC-transplanted thrombi were 100%,230.7%,and 212.5% of levels detected in the sham-operated group(P<0.01),and 99.9%,215.4%,and 177.8% of levels detected in the experimental control group(P<0.01).VEGF,ANG-1 and MCP-1 protein levels exhibited a similar trend.Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization.

  15. AI-05IMPACT OF GBM MICROENVIRONMENT ON EXPRESSION PROFILE OF BONE MARROW DERIVED PROGENITOR CELLS

    OpenAIRE

    Burrell, Kelly; Singh, Sanjay; Agnihotri, Sameer; Hill, Richard; Aldape, Kenneth; Zadeh, Gelareh

    2014-01-01

    We have recently shown that bone marrow derived cells (BMDC) provide a distinct tumor region dependent contribution to glioblastoma multiforme (GBM) neovascularization. The influence of GBM microenvironment on differentiation and modulation of expression factors by BMDC however remains unknown. In this study we establish the differential expression profile of BMDC as a consequence of recruitment and interaction with the GBM microenvironment and in response to radiation (RTx) and anti-angiogen...

  16. Effect of Spatholobus suberectus Dunn on proliferation of progenitor cells in mice with bone marrow depression

    Institute of Scientific and Technical Information of China (English)

    Chen Donghui; Luo Xia; Yu Mengyao; Zhao Yiqing; Yang Zhirong

    2005-01-01

    AIM: To study the effect of Spatholobus suberectus Dunn on the proliferation and hematonic mechanism of Spatholobus suberectus Dunn. Methods: The techniques of culture of hematopoietic cell and hematopoietic growth factor (HGF) assay were used. The method of semi-solid culture with methylcellulose of CFU-GM, CFU-E, BFU-E,CFU-Meg was adopted in bone marrow depressed mice which treated with Spatholobus suberectus Dunn for a long time. Results: Spatholobus suberectus Dunn could obviously promote the proliferation of bone marrow cells and spleen lymphocytes in healthy and anaemic mice. The culture medium of spleen cell, macrophage, lung and skeletal muscle treated with Spatholobus suberectus Dunn had much stronger stimulating effects on hematopoietic cells. The numbers of CFU-GM, CFU-E,BFU-E,CFU-Meg in bone marrow depressed mice were raised distinctly under the control of Spatholobus suberectus Dunn as compared with those of contrast group. Conclusions: Spatholobus suberectus Dunn may enhance hematopoiesis by stimulating directly and/or indirectly stroma cell in hematopoietic inductive microenvironment and muscle tissue to secrete some HGF (Epo, GM-CSF, IL, and MK-CSF). It can promote the proliferation and differentiation of hematopoietic cells in anaemic mice. This is one of the biological mechanisms for hematonic effect of Spatholobus suberectus Dunn.

  17. Uncaria tomentosa extract increases the number of myeloid progenitor cells in the bone marrow of mice infected with Listeria monocytogenes.

    Science.gov (United States)

    Eberlin, Samara; dos Santos, Leonilda M B; Queiroz, Mary L S

    2005-07-01

    In this study, we demonstrated that Uncaria tomentosa extract (UTE) protects mice from a lethal dose of Listeria monocytogenes when administered prophylactically at 50, 100, 150 and 200 mg/kg for 7 days, with survival rates up to 35%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with L. monocytogenes, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Non-infected mice treated with 100 mg/kg UTE also presented higher numbers of CFU-GM in the bone marrow than the controls. Investigation of the production of colony-stimulating factors revealed increased colony-stimulating activity (CSA) in the serum of normal and infected mice pre-treated with UTE. Moreover, stimulation of myelopoiesis and CSA occurred in a dose-dependent manner, a plateaux being reached with the dose of 100 mg/kg. Further studies to investigate the levels of factors such as IL-1 and IL-6 were undertaken. We observed increases in the levels of IL-1 and IL-6 in mice infected with L. monocytogenes and treated with 100 mg/kg of UTE. White blood cells (WBC) and differential counting were also performed, and our results demonstrated no significant changes in these data, when infected mice were pre-treated with 100 mg/kg of UTE. All together, our results suggest that UTE indirectly modulates immune activity and probably disengages Listeria-induced supression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1 and IL-6).

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

    Science.gov (United States)

    2016-01-01

    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. PMID:27840829

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Effects of Simian Betaretrovirus Serotype 1 (SRV1) Infection on the Differentiation of Hematopoietic Progenitor Cells (CD34+) Derived from Bone Marrow of Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Montiel, Nestor A; Todd, Patricia A; Yee, JoAnn; Lerche, Nicholas W

    2012-01-01

    Peripheral blood cytopenias, particularly persistent anemia and neutropenia, are commonly associated with simian betaretrovirus infection of Asian monkeys of the genus Macaca. The pathogenetic mechanisms underlying these hematologic abnormalities are not well understood. The current study investigated the in vitro tropism of simian betaretrovirus (SRV) for both hematopoietic progenitor (CD34+) and stromal cells obtained from rhesus macaque bone marrow and assessed the effects of infection on hematopoietic progenitor cell differentiation in vitro. After in vitro exposure, SRV proviral DNA could be demonstrated by real-time PCR in cells and the reverse transcriptase assay in supernatants from SRV-exposed progenitor-associated stroma, but not in differentiated colonies derived from SRV-exposed progenitors. Furthermore, in vitro exposure involving cell–cell contact of uninfected CD34+ progenitor cells with SRV-infected stromal cells resulted in a statistically significant reduction in granulocyte–macrophage colony formation in absence of detectable SRV-infection of progenitor cells. Reduction in colony formation occurred in a ‘dose-dependent’ fashion with increasing contact time. No effects on erythroid lineages and RBC differentiation were noted. Our results suggest that hematologic abnormalities observed during SRV disease (natural or experimental) of rhesus macaques may not result from direct effects of viral infection of progenitor cell populations, but rather be (at least in part) a consequence of SRV infection of supportive bone marrow stroma with secondary effects on differentiation of associated progenitor cells. PMID:22330653

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Endocannabinoids are expressed in bone marrow stromal niches and play a role in interactions of hematopoietic stem and progenitor cells with the bone marrow microenvironment.

    Science.gov (United States)

    Jiang, Shuxian; Zagozdzon, Radoslaw; Jorda, Meritxell Alberich; Parmar, Kalindi; Fu, Yigong; Williams, John S; Wood, Jodi Anne T; Makriyannis, Alexandros; Banu, Naheed; Avraham, Shalom; Groopman, Jerome E; Avraham, Hava Karsenty

    2010-11-12

    Endocannabinoids are lipid signaling molecules that act via G-coupled receptors, CB(1) and CB(2). The endocannabinoid system is capable of activation of distinct signaling pathways on demand in response to pathogenic events or stimuli, hereby enhancing cell survival and promoting tissue repair. However, the role of endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are maintained in the quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signaling. We report that HSPCs express the CB(1) receptors and that BM stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/10(7) cells), and 2-AG (75.2 ng/10(7) cells). In response to the endotoxin lipopolysaccharide (LPS), elevated levels of AEA (75.6 pg/10(7) cells) and 2-AG (98.8 ng/10(7) cells) were secreted from BM stromal cells, resulting in migration and trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore, administration of exogenous cannabinoid CB(1) agonists in vivo induced chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid receptor knock-out mice Cnr1(-/-) showed a decrease in side population (SP) cells, whereas fatty acid amide hydrolase (FAAH)(-/-) mice, which have elevated levels of AEA, yielded increased colony formation as compared with WT mice. In addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids and was inhibited by specific cannabinoid antagonists as well as impaired in cannabinoid receptor knock-out mice Cnr1(-/-), as compared with WT mice. Thus, we propose a novel function of the endocannabinoid system, as a regulator of HSPC interactions with their BM niches, where endocannabinoids are expressed in HSC niches and under stress conditions, endocannabinoid expression levels are enhanced to induce HSPC migration for proper hematopoiesis.

  3. Principles of bone marrow processing and progenitor cell/mononuclear cell concentrate collection in a continuous flow blood cell separation system.

    Science.gov (United States)

    Hester, J P; Rondón, G; Huh, Y O; Lauppe, M J; Champlin, R E; Deisseroth, A B

    1995-08-01

    The application of continuous flow apheresis technology to processing bone marrow for collection of the mononuclear progenitor cell population appears to follow the same principles as collection of mononuclear cells from peripheral blood. Unlike peripheral blood, however, where mobilization of cells from extravascular sites during the procedures contributes significantly to the final cell yield, the entire quantity of progenitor cells available for recovery from marrow is present in the original marrow when it is pooled. The process then becomes one of attempting optimal recovery of the cells of interest while excluding contaminating erythrocytes and cells of the myeloid series. This study reports the development of a protocol for recovery of MNC, CD33+, CD34+, and CD34+/DR- cells from harvested marrow for autologous and allogeneic transplants using a continuous flow blood cell separator, the variables influencing the recovery of the cells of interest and the clinical response to infusion of the processed cells.

  4. 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

  5. Registered report: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.

    Science.gov (United States)

    Lesnik, Jake; Antes, Travis; Kim, Jeewon; Griner, Erin; Pedro, Luisa

    2016-01-29

    The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET" by Peinado and colleagues, published in Nature Medicine in 2012 (Peinado et al., 2012). The key experiments being replicated are from Figures 4E, as well as Supplementary Figures 1C and 5A. In these experiments, Peinado and colleagues show tumor exosomes enhance metastasis to bones and lungs, which is diminished by reducing Met expression in exosomes (Peinado et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

  6. Bone marrow stem/progenitor cell mobilization in C57BL/6J and BALB/c mice.

    Science.gov (United States)

    Lee, Hakmo; Che, Jeong-Hwan; Oh, Ju Eun; Chung, Sung Soo; Jung, Hye Seung; Park, Kyong Soo

    2014-03-01

    Bone marrow (BM) has been considered as a reservoir of stem/progenitor cells which are able to differentiate into ectodermal, endodermal, and mesodermal origins in vitro as well as in vivo. Following adequate stimulation, such as granulocyte stimulating factor (G-CSF) or AMD3100, BM resident stem/progenitor cells (BMSPCs) can be mobilized to peripheral blood. Several host-related factors are known to participate in this mobilization process. In fact, a significant number of donors are resistant to G-CSF induced mobilization protocols. AMD3100 is currently used in combination with G-CSF. However, information regarding host-related factors which may influence the AMD3100 directed mobilization is extremely limited. In this study, we were to get some more knowledge on the host-related factors that affect the efficiency of AMD3100 induced mobilization by employing in vivo mobilization experiments. As a result, we found that C57BL/6J mice are more sensitive to AMD3100 but less sensitive to G-CSF which promotes the proliferation of BMSPCs. We excluded S1P as one of the host related factor which influences AMD3100 directed mobilization because pre-treatment of S1P receptor antagonist FTY720 did not inhibit BMSPC mobilization. Further in vitro experiments revealed that BALB/c mice, compared to C57BL/6J mice, have less BMSPCs which migrate in response to host related factors such as sphingosine-1-phosphate (S1P) and to CXCL12. We conclude that AMD3100-directed mobilization depends on the number of BMSPCs rather than on the host-related factors. These results suggest that the combination of AMD3100 and G-CSF is co-operative and is optimal for the mobilization of BMSPCs.

  7. Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells.

    Science.gov (United States)

    Chen, Hongfeng; Titushkin, Igor; Stroscio, Michael; Cho, Michael

    2007-02-15

    Functionalized quantum dots offer several advantages for tracking the motion of individual molecules on the cell surface, including selective binding, precise optical identification of cell surface molecules, and detailed examination of the molecular motion without photobleaching. We have used quantum dots conjugated with integrin antibodies and performed studies to quantitatively demonstrate changes in the integrin dynamics during osteogenic differentiation of human bone marrow derived progenitor cells (BMPCs). Consistent with the unusually strong BMPC adhesion previously observed, integrins on the surface of undifferentiated BMPC were found in clusters and the lateral diffusion was slow (e.g., approximately 10(-11) cm2/s). At times as early as those after a 3-day incubation in the osteogenic differentiation media, the integrin diffusion coefficients increased by an order of magnitude, and the integrin dynamics became indistinguishable from that measured on the surface of terminally differentiated human osteoblasts. Furthermore, microfilaments in BMPCs consisted of atypically thick bundles of stress fibers that were responsible for restricting the integrin lateral mobility. Studies using laser optical tweezers showed that, unlike fully differentiated osteoblasts, the BMPC cytoskeleton is weakly associated with its cell membrane. Based on these findings, it appears likely that the altered integrin dynamics is correlated with BMPC differentiation and that the integrin lateral mobility is restricted by direct links to microfilaments.

  8. Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function

    Science.gov (United States)

    Halvarsson, Camilla; Eliasson, Pernilla

    2017-01-01

    Background Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types. It has not been established whether PDK1 is essential for HSC function and mediates hypoxia-adapting functions in HSCs. While the Pdk gene family contains four members (Pdk1-4), it was recently shown that Pdk2 and Pdk4 have an important role in regulating LT-HSCs. Principle findings Here we demonstrate that PDK1 activity is crucial for transplantable HSC function. Whereas Pdkl, Pdk2, and Pdk3 transcripts were expressed at higher levels in different subtypes of HSCs compared to differentiated cells, we could not detect any major differences in expression between LT-HSCs and more short-term HSCs and multipotent progenitors. When studying HIF-1α-mediated regulation of Pdk activity in vitro, Pdk1 was the most robust target regulated by hypoxia, whereas Pdk2, Pdk3, and Pdk4 were not affected. Contrary, genetic ablation in a cre-inducible Hif-1α knockout mouse did not support a link between HIF-1α and Pdk1. Silencing of Pdk1 by shRNA lentiviral gene transfer partially impaired progenitor colony formation in vitro and had a strong negative effect on both long-term and short-term engraftment in mice. Conclusions Our study demonstrates that PDK1 has broad effects in hematopoiesis and is a critical factor for engraftment of both HSCs and multipotent progenitors upon transplantation to recipient mice. While Pdk1 was a robust hypoxia-inducible gene

  9. A novel and feasible way to cultivate and purify endothelial progenitor cells from bone marrow of children with congenital heart diseases

    Institute of Scientific and Technical Information of China (English)

    WU Yong-tao; LI Jing-xing; LIU Shuo; XIN Yi; WANG Zi-jian; GAO Jin; JI Bing-yang; FAN Xiang-ming; ZHOU Qi-wen

    2012-01-01

    Background Endothelial progenitor cells (EPCs) are used in vascular tissue engineering and clinic therapy.Some investigators get EPCs from the peripheral blood for clinic treatment,but the number of EPCs is seldom enough.We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease,to provide enough seed cells for a small calibre vascular tissue engineering study.Methods The 0.5-ml of bone marrow was separated from the sternum bone,and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery.CD34+ and CD34+/VEGFR+cells in the bone marrow and peripheral blood were quantified by flow cytometry.CD34+NEGFR+ cells were defined as EPCs.Mononuclear cells in the bone marrow were isolated by Ficoll(R) density gradient centrifugation and cultured by the EndoCult Liquid Medium KitTM.Colony forming endothelial cells was detected.Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells.Results CD34+ and CD34+NEGFR+ cells in peripheral blood were (0.07±0.05)% and (0.05±0.02)%,respectively.The number of CD34+ and CD34+NEGFR+ cells in bone marrow were significantly higher than in blood,(4.41±1.47)% and (0.98±0.65)%,respectively (P <0.0001).Many colony forming units formed in the culture.These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-1.Conclusion This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease,and provide seed cells for small calibre vascular tissue engineering.

  10. 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 ...

  11. Human Bone Marrow Mesenchymal Progenitors: Perspectives on an Optimized In Vitro Manipulation

    Directory of Open Access Journals (Sweden)

    Eric eCordeiro-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.

  12. An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

    Institute of Scientific and Technical Information of China (English)

    黄晓军; 郭乃榄; 任汉云; 张耀臣; 高志勇; 陆道培

    2003-01-01

    Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

  13. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses.

    Science.gov (United States)

    Bellini, Alberto; Mattoli, Sabrina

    2007-09-01

    Human fibrocytes are mesenchymal progenitors that exhibit mixed morphological and molecular characteristics of hematopoietic stem cells, monocytes and fibroblasts. They likely represent the obligate intermediate stage of differentiation into mature mesenchymal cells of a bone marrow-derived precursor of the monocyte lineage under permissive conditions. On in vitro stimulation with pro-fibrotic cytokines and growth factors, human fibrocytes produce large quantities of extracellular matrix components and further differentiate into cells identical to the contractile myofibroblasts that emerge at the tissue sites during repair processes and in some fibrotic lesions. Studies in various animal models of wound healing or fibrotic diseases have confirmed the ability of fibrocytes to differentiate into mature mesenchymal cells in vivo and have suggested a causal link between fibrocyte accumulation and ongoing tissue fibrogenesis or vascular remodeling in response to tissue damage or hypoxia. Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in human hypertrophic scars, in the skin of patients affected by nephrogenic systemic fibrosis, in human atherosclerotic lesions, and in pulmonary diseases characterized by repeated cycles of inflammation and repair, like asthma. The presence of fibrocyte-like cells has been reported in human chronic pancreatitis and chronic cystitis. Similar cells also populate the stroma surrounding human benign tumors. The available data indicate that human fibrocytes serve as a source of mature mesenchymal cells during reparative processes and in fibrotic disorders or stromal reactions predominantly associated with a persistent inflammatory infiltrate or with the selective recruitment of monocytes induced by ischemic changes and tumor development. A deeper understanding of the mechanisms involved in fibrocyte differentiation in these pathological conditions may lead to the development of novel therapies for

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

    Science.gov (United States)

    Colnot, C; Huang, S; Helms, J

    2006-11-24

    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.

  15. Mesangiogenic Progenitor Cells Derived from One Novel CD64brightCD31brightCD14neg Population in Human Adult Bone Marrow

    Science.gov (United States)

    Barachini, Serena; Montali, Marina; Carnicelli, Vittoria; Fazzi, Rita; Parchi, Paolo; Petrini, Mario

    2016-01-01

    Mesenchymal stromal cells (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. Nonetheless, the unambiguous identification of a unique in vivo MSC progenitor is still lacking, and the hypothesis that these multipotent cells could possibly arise from different in vivo precursors has been gaining consensus in the last years. We identified a novel multipotent cell population in human adult bone marrow that we first named Mesodermal Progenitor Cells (MPCs) for the ability to differentiate toward the mesenchymal lineage, while still retaining angiogenic potential. Despite extensive characterization, MPCs positioning within the differentiation pathway and whether they can be ascribed as possible distinctive progenitor of the MSC lineage is still unclear. In this study, we describe the ex vivo isolation of one novel bone marrow subpopulation (Pop#8) with the ability to generate MPCs. Multicolor flow cytometry in combination with either fluorescence-activated cell sorting or magnetic-activated cell sorting were applied to characterize Pop#8 as CD64brightCD31brightCD14neg. We defined Pop#8 properties in culture, including the potential of Pop#8-derived MPCs to differentiate into MSCs. Gene expression data were suggestive of Pop#8 in vivo involvement in hematopoietic stem cell niche constitution/maintenance. Pop#8 resulted over three logs more frequent than other putative MSC progenitors, corroborating the idea that most of the controversies regarding culture-expanded MSCs could be the consequence of different culture conditions that select or promote particular subpopulations of precursors. PMID:26975798

  16. Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells.

    Science.gov (United States)

    Broxmeyer, H E; Sherry, B; Lu, L; Cooper, S; Oh, K O; Tekamp-Olson, P; Kwon, B S; Cerami, A

    1990-09-15

    Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1 alpha, 1 beta, and 2 were assessed for effects on murine (mu) and human (hu) marrow colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies. Recombinant MIP-1 alpha, -1 beta, and -2 enhanced muCFU-GM colonies above that stimulated with 10 to 100 U natural mu macrophage-colony-stimulating factor (M-CSF) or rmuGM-CSF, with enhancement seen on huCFU-GM colony formation stimulated with suboptimal rhuM-CSF or rhuGM-CSF; effects were neutralized by respective MIP-specific antibodies. Macrophage inflammatory proteins had no effects on mu or huBFU-E colonies stimulated with erythropoietin (Epo). However, natural MIP-1 and rMIP-1 alpha, but not rMIP-1 beta or -2, suppressed muCFU-GM stimulated with pokeweed mitogen spleen-conditioned medium (PWMSCM), huCFU-GM stimulated with optimal rhuGM-CSF plus rhu interleukin-3 (IL-3), muBFU-E and multipotential progenitors (CFU-GEMM) stimulated with Epo plus PWMSCM, and huBFU-E and CFU-GEMM stimulated with Epo plus rhuIL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1 alpha were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34 HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75%. These results, along with our previous studies, suggest that MIP-1 alpha, -1 beta, and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1 alpha may have direct suppressing activity for more immature progenitors.

  17. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model.

    Science.gov (United States)

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil; Muschler, George F

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone

  18. Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi-directional loss of heterozygosity in bone marrow progenitors.

    Science.gov (United States)

    Shetzer, Yoav; Napchan, Yael; Kaufman, Tom; Molchadsky, Alina; Tal, Perry; Goldfinger, Naomi; Rotter, Varda

    2017-03-15

    p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li-Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune-system and p53 LOH. Previously, we reported that p53 heterozygous bone-marrow mesenchymal progenitor cells undergo p53 LOH in-vivo. Surprisingly, the loss of either the wild-type p53 allele or mutant p53 allele was detected with a three-to-one ratio in favor of losing the mutant allele. In this study, we examined whether the immune-system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune-deficient mice exhibited the same preference of losing the mutant p53 allele as immune-competent matched cells, nevertheless, these animals showed a significantly shorter tumor-free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune-deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune-competent mice. These findings indicate that the immune-system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune-system may recognize and clear cells that underwent p53 LOH, whereas in immune-compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune-system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.

  19. Effect of hydroxyurea and etoposide on transduction of human bone marrow mesenchymal stem and progenitor cell by adeno-associated virus vectors

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong JU; Si-quan LOU; Wei-guo WANG; Jian-qiang PENG; Hua TIAN

    2004-01-01

    AIM: To study the effect of hydroxyurea and etoposide on transduction of human marrow mesenchymal and progenitor stem cells by adeno-associated virus (AAV). METHODS: Isolated human bone marrow mesenchymal stem and progenitor cells (hMSCs) were cultured in DMEM containing 10 % FBS or 5 % FBS and dexamethasone 1 μmol/L respectively. After being treated with hydroxyurea and etoposide, hMSCs were transduced by AAV-LUC.After two days luciferase activity (relative light unites per second or RLU/s) were tested, which indirectly reflected the relative transduction efficiency of different groups, and virus DNA was isolated by Hirt extraction for Southern hybridization. RESULTS: Transduction luciferase activity and transduction efficiency in cultures treated with hydroxyurea and etoposide were significantly higher than that in control cultures. Dividing cells had about 20-fold higher transduction efficiency compared with control cells. Transduction efficiency in stationary cells was about 50 times higher than that in control cells. Southern analysis showed that hydroxyurea and etoposide enhanced second-strand DNA synthesis by rAAV. CONCLUSION: Hydroxyurea and etoposide could increase transduction efficiency of hMSCs by AAV vectors, and stationary cells were more sensitive to these drugs than dividing cells.

  20. 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.

  1. 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 graft-

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

    Energy Technology Data Exchange (ETDEWEB)

    Aguirre, A.; Planell, J.A. [Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 15-21, 08028 Barcelona (Spain); Dept. of Material Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); CIBER-BBN, Maria de Luna 11, Ed. CEEI, 50118 Zaragoza (Spain); Engel, E., E-mail: elisabeth.engel@upc.edu [Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 15-21, 08028 Barcelona (Spain); Dept. of Material Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); CIBER-BBN, Maria de Luna 11, Ed. CEEI, 50118 Zaragoza (Spain)

    2010-09-17

    Research highlights: {yields} BM-EPCs and MSCs establish complex, self-organizing structures in co-culture. {yields} Co-culture decreases proliferation by cellular self-regulatory mechanisms. {yields} Co-cultured cells present an activated proangiogenic phenotype. {yields} 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.

  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. Effect of Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Endothelial Progenitor Cells on Myocardial Ischemia-reperfusion Injury in Mini-swine

    Institute of Scientific and Technical Information of China (English)

    Chong-jian Li; Ji-lin Chen; Jian-jun Li; Run-lin Gao; Yue-jin Yang; Feng-huan Hu; Wei-xian Yang; Shi-jie You; Lai-feng Song; Ying-mao Ruan; Shu-bin Qiao

    2010-01-01

    Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mono-nuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model.Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About (3.54+0.90)x108 bone marrow mononudear cells (MNC group, n=9) or (1.16± 1.07)×10 endothelial progenitor cells (EPC group, n=7) was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control (n=7). Echocardio-graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc-tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope.Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively (P0.05). EPC decreased total infarction size more than MNC did (1.60±0.26 cm vs. 3.71±1.38 cm, P<0.05). Undermature endothelial cells and myocytes were found under transmission electromicroscope.Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function, Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit fibrogenesis, and differentiate into myocardial cells.

  5. Archival bone marrow samples

    DEFF Research Database (Denmark)

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata;

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole...... with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP...

  6. Bone Marrow-Derived Macrophages (BMM)

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Porse, Bo

    2008-01-01

    of committed myeloid progenitors into cells of the macrophage/monocyte lineage. Mice lacking functional M-CSF are deficient in macrophages and osteoclasts and suffer from osteopetrosis. In this protocol, bone marrow cells are grown in culture dishes in the presence of M-CSF, which is secreted by L929 cells...

  7. The effects of GM1 and Bfgf synergistically inducing adult rat bone marrow stromal cells to form neural progenitor cells and their differentiation

    Institute of Scientific and Technical Information of China (English)

    张卉; 王纪佐; 孙红宇; 张建宁; 杨树源

    2004-01-01

    Objective: To investigate the effects of GM1 on inducing adult rat bone marrow stromal cells(MSCs) to form neural progenitor cells and their differentiation. Methods: Purified MSCs were induced by different components of basic fibroblast growth factor (bFGF) alone, GM1 alone or combination of bFGF with GM1. After 3 days' incubation, fibronectin and collagen I were detected with immunocytochemistry, and nestin was detected with immunofluorescence. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and galactose cerebroside (GalC) were detected with immunocytochemistry after 7 days' incubation. Results: After induction with bFGF alone or combination of bFGF and GM1, some MSCs exhibited the phenotypes of neural progenitor cells, and then neurons and astrocytes. In these two groups, the positive cells for fibronectin and collagen I decreased markedly after 3 days' induction. At the same time, the positive cells for nestin increased markedly. After 7 days' induction, NSE and GFAP-positive cells increased significantly. Furthermore, the addition of bFGF and GM1 caused the maximal variation. However, addition of GM1 alone had no inductive effects.Conclusions: Combination of bFGF with GM1 may synergistically promote the transformation of MSCs and differentiation into neurons and astrocyte-like cells. The results suggest a promising route for the application of MSCs.

  8. Double expression of CD34 and CD117 on bone marrow progenitors is a hallmark of the development of functional mast cell of Callithrix jacchus (common marmoset).

    Science.gov (United States)

    Nunomura, Satoshi; Shimada, Shin; Kametani, Yoshie; Yamada, Yuko; Yoshioka, Mino; Suemizu, Hiroshi; Ozawa, Manabu; Itoh, Toshio; Kono, Azumi; Suzuki, Ryuji; Tani, Kenzaburo; Ando, Kiyoshi; Yagita, Hideo; Ra, Chisei; Habu, Sonoko; Satake, Masanobu; Sasaki, Erika

    2012-09-01

    Mast cells (MCs) are developed from hematopoietic progenitor cells and play an important role in inflammation. Study of the kinetics of development and accumulation of primate MC in vivo is crucial for the control of human inflammatory diseases, as evolution of the immune system is quite rapid and inflammation including MC response is considered to be different between mouse and human. In the present study, we examined the development of MC from hematopoietic progenitors of Callithrix jacchus (common marmoset), an experimental animal of nonhuman primates. Bone marrow cells were fractionated for the expression of CD34 and CD117 by cell sorting. MCs were developed in vitro or by transplanting the cells to NOD/SCID/IL-2γc knockout (NOG) mice. In vitro culture of CD34(+)CD117(+) (double positive, DP) cells with stem cell factor could generate high-affinity Fc epsilon receptor (FcεR)-expressing CD117(+) cells with typical granules. The developed MC released β-hexosaminidase and produced leukotriene C(4) after the stimulation of FcεRI. Transplantation of DP cells gave rise to a marked expansion of CD34(-)CD45(+)CD117(+)FcεR(+) cells in NOG mice. They expressed transcripts encoding chymase 1 and tryptase β. Differentiation of CD34(-)CD117(+) cells to MCs was relatively limited compared with the DP cells, similarly to human MCs. These results suggest that this marmoset system provides a good model for human MC development.

  9. Sonic hedgehog protein promotes bone marrow-derived endothelial progenitor cell proliferation, migration and VEGF production via PI 3-kinase/ Akt signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Jin-rong FU; Wen-li LIU; Jian-feng ZHOU; Han-ying SUN; Hui-zhen XU; Li LUO; Heng ZHANG; Yu-feng ZHOU

    2006-01-01

    Aim: To investigate the effects of Sonic hedgehog (shh) protein on bone marrowderived endothelial progenitor cells (BM-EPC) proliferation, migration and vascular endothelial growth factor (VEGF) production, and the potential signaling pathways involved in these effects. Methods: Bone marrow-derived Flk-l+ cells were enriched using the MACS system from adult Kunming mice and then BM-EPC was cultured in gelatin-coated culture dishes. The effects of shh N-terminal peptide on BM-EPC proliferation were evaluated using the MTT colorimetric assay. Cell migration was assayed using a modified Boyden chamber technique. The production of VEGF was determined by ELIS A and immunofluorescence analysis. The potential involvement of PKC and PI3K signaling pathways was explored using selective inhibitor or Western blot. Results: The proliferation, migration and VEGF production in BM-EPC could be promoted by endogenous shh Nterminal peptide at concentrations of 0.1 μg/mL to 10 ug/mL, and could be inhibited by anti-shh antibodies. Shh-mediated proliferation and migration in BM-EPC could be partly attenuated by anti-VEGF. Phospho-PI3-kinase expression in newly separated BM-EPC was low, and it increased significantly when exogenous shh N-terminal peptide was added, but could be attenuated by anti-human/mouse shh N-terminal peptide antibody. Moreover, the inhibitor of the PI3-kinase, but not the inhibitor of the PKC, significantly inhibited the shh-mediated proliferation, migration and VEGF production. Conclusion: Shh protein can stimulate bone marrow-derived BM-EPC proliferation, migration and VEGF production, which may promote neovascularization to ischemic tissues. This results also suggests that the PI3-kinase/Akt signaling pathways are involved in the angiogenic effects of shh.

  10. Stage-specific roles for CXCR4 signaling in murine hematopoietic stem/progenitor cells in the process of bone marrow repopulation.

    Science.gov (United States)

    Lai, Chen-Yi; Yamazaki, Satoshi; Okabe, Motohito; Suzuki, Sachie; Maeyama, Yoshihiro; Iimura, Yasuaki; Onodera, Masafumi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Otsu, Makoto; Nakauchi, Hiromitsu

    2014-07-01

    Hematopoietic cell transplantation has proven beneficial for various intractable diseases, but it remains unclear how hematopoietic stem/progenitor cells (HSPCs) home to the bone marrow (BM) microenvironment, initiate hematopoietic reconstitution, and maintain life-long hematopoiesis. The use of newly elucidated molecular determinants for overall HSPC engraftment should benefit patients. Here, we report that modification of C-X-C chemokine receptor type 4 (Cxcr4) signaling in murine HSPCs does not significantly affect initial homing/lodging events, but leads to alteration in subsequent BM repopulation kinetics, with observations confirmed by both gain- and loss-of-function approaches. By using C-terminal truncated Cxcr4 as a gain-of-function effector, we demonstrated that signal augmentation likely led to favorable in vivo repopulation of primitive cell populations in BM. These improved features were correlated with enhanced seeding efficiencies in stromal cell cocultures and altered ligand-mediated phosphorylation kinetics of extracellular signal-regulated kinases observed in Cxcr4 signal-augmented HSPCs in vitro. Unexpectedly, however, sustained signal enhancement even with wild-type Cxcr4 overexpression resulted in impaired peripheral blood (PB) reconstitution, most likely by preventing release of donor hematopoietic cells from the marrow environment. We thus conclude that timely regulation of Cxcr4/CXCR4 signaling is key in providing donor HSPCs with enhanced repopulation potential following transplantation, whilst preserving the ability to release HSPC progeny into PB for improved transplantation outcomes.

  11. TNF-TNFR2/p75 signaling inhibits early and increases delayed nontargeted effects in bone marrow-derived endothelial progenitor cells.

    Science.gov (United States)

    Sasi, Sharath P; Song, Jin; Park, Daniel; Enderling, Heiko; McDonald, J Tyson; Gee, Hannah; Garrity, Brittany; Shtifman, Alexander; Yan, Xinhua; Walsh, Kenneth; Natarajan, Mohan; Kishore, Raj; Goukassian, David A

    2014-05-16

    TNF-α, a pro-inflammatory cytokine, is highly expressed after being irradiated (IR) and is implicated in mediating radiobiological bystander responses (RBRs). Little is known about specific TNF receptors in regulating TNF-induced RBR in bone marrow-derived endothelial progenitor cells (BM-EPCs). Full body γ-IR WT BM-EPCs showed a biphasic response: slow decay of p-H2AX foci during the initial 24 h and increase between 24 h and 7 days post-IR, indicating a significant RBR in BM-EPCs in vivo. Individual TNF receptor (TNFR) signaling in RBR was evaluated in BM-EPCs from WT, TNFR1/p55KO, and TNFR2/p75KO mice, in vitro. Compared with WT, early RBR (1-5 h) were inhibited in p55KO and p75KO EPCs, whereas delayed RBR (3-5 days) were amplified in p55KO EPCs, suggesting a possible role for TNFR2/p75 signaling in delayed RBR. Neutralizing TNF in γ-IR conditioned media (CM) of WT and p55KO BM-EPCs largely abolished RBR in both cell types. ELISA protein profiling of WT and p55KO EPC γ-IR-CM over 5 days showed significant increases in several pro-inflammatory cytokines, including TNF-α, IL-1α (Interleukin-1 alpha), RANTES (regulated on activation, normal T cell expressed and secreted), and MCP-1. In vitro treatments with murine recombinant (rm) TNF-α and rmIL-1α, but not rmMCP-1 or rmRANTES, increased the formation of p-H2AX foci in nonirradiated p55KO EPCs. We conclude that TNF-TNFR2 signaling may induce RBR in naïve BM-EPCs and that blocking TNF-TNFR2 signaling may prevent delayed RBR in BM-EPCs, conceivably, in bone marrow milieu in general.

  12. Migration and differentiation of bone marrow-derived multipotent adult progenitor cells through tail vein injection in a rat model of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Lei Lei; Ruixiang Zhou

    2009-01-01

    BACKGROUND: Multipotent adult progenitor cells (MAPCs) from the bone marrow have been shown to differentiate into neurons.OBJECTIVE: To observe migration, survival, and neuronal-like differentiation of MAPCs by tail vein injection.DESIGN, TIME AND SETTING: Randomized, controlled experiment of neural tissue engineering was performed at the Laboratory for Cardio-Cerebrovascular Disease, Hospital of Integrated Traditional and Western Medicine, Tongji Medical College of Huazhong University of Science and Technology between September 2006 and August 2007.MATERIALS: Eighty Sprague Dawley rats, 3-6 months old, underwent cerebral ischemia/reperfusion by thread technique, and were randomly divided into model and MAPCs groups (n = 40).METHODS: Mononuclear cells were harvested from bone marrow using the Ficoll-Paque density gradient centrifugation method. After removing CD45 and glycophorin A-positive cells (GLYA+) with immunomagnetic beads, CD45 GLYA adult progenitor cells were labeled with bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU). A total of 1 mL cell suspension, containing 5 ×106 MAPCs, was injected into the MAPCs group through the tail vein. A total of 1 mL normal saline was injected into the model rats.MAIN OUTCOME MEASURES: After 60 days, BrdU and neuron-specific enolase double-positive cells were observed using immunofluorescence. Cell morphology was observed under electron microscopy, and nerve growth factor mRNA was measured through RT-PCR. In addition, rat neurological functions were measured with behavioral tests.RESULTS: Immunofluorescence revealed that MAPCs positive for BrdU and neuron specific enolase were found surrounding the ischemic focus in the MAPCs group. Microscopic observation suggested that MAPCs-derived neuronal-like cells connected with other nerve cells to form synapses, Compared with the model animals, the level of nerve growth factor mRNA was significantly upregulated in rats injected with MAPCs (P < 0.05). In addition, rats in the MAPCs

  13. Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis.

    Science.gov (United States)

    Murray, L J; Luens, K M; Estrada, M F; Bruno, E; Hoffman, R; Cohen, R L; Ashby, M A; Vadhan-Raj, S

    1998-03-01

    Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on

  14. Reactivity of murine cytokine fusion toxin, diphtheria toxin390-murine interleukin-3 (DT390-mIL-3), with bone marrow progenitor cells.

    Science.gov (United States)

    Chan, C H; Blazar, B R; Greenfield, L; Kreitman, R J; Vallera, D A

    1996-08-15

    Myeloid leukemias can express interleukin-3 receptors (IL-3R). Therefore, as an antileukemia drug, a fusion immunotoxin was synthesized consisting of the murine IL-3 (mIL-3) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mIL-3 hybrid gene was cloned into a vector under the control of an inducible promote. The fusion protein was expressed in Escherichia coli and then purified from inclusion bodies. The fusion toxin was potent because it inhibited FDC-P1, an IL-3R-expressing murine myelomonocytic tumor line (IC50 = 0.025 nmol/L or 1.5 ng/mL). Kinetics were rapid and cell-free studies showed that DT390-mIL-3 was as toxic as native DT. DT390-mIL-3 was selective because anti-mIL-3 monoclonal antibody, but not irrelevant antibody, inhibited its ability to kill. Cell lines not expressing IL-3R were not inhibited by the fusion protein. Because the use of DT390-mIL-3 as an antileukemia agent could be restricted by its reactivity with committed and/or primitive progenitor cells, bone marrow (BM) progenitor assays were performed. DT390-mIL-3 selectively inhibited committed BM progenitor cells as measured by in vitro colony-forming unit-granulocyte-macrophage and in vivo colony-forming unit-spleen colony assays. To determine if this fusion protein was reactive against BM progenitor cells required to rescue lethally irradiated recipients, adoptive transfer experiments were performed. Eight million DT390-mIL-3-treated C57BL/6 Ly5.2 BM cells, but not 4 million, were able to rescue lethally irradiated congenic C57BL/6 Ly5.1 recipients, suggesting that progenitor cells might be heterogenous in their expression of IL-3R. This idea was supported in competitive repopulation experiments in which DT390-mIL-3 treated C57BL/6 Ly5.2 BM cells were mixed with nontreated C57BL/6 Ly5.1 BM cells and used to reconstitute C57BL/6 Ly5.1 mice. A significant reduction

  15. Bone marrow CD34+ progenitor cells from HIV infected patients show an impaired T cell differentiation potential related to pro-inflammatory cytokines.

    Science.gov (United States)

    Bordoni, Veronica; Bibas, Michele; Viola, Domenico; Sacchi, Alessandra; Cimini, Eleonora; Tumino, Nicola; Casetti, Rita; Amendola, Alessandra; Ammassari, Adriana; Agrati, Chiara; Martini, Federico

    2017-01-26

    The impact of HIV infection on the frequency and differentiation capability of CD34+ Bone Marrow Hematopoietic Progenitor Cells (BM-HPCs) is still debated, having a possible primary role in antiretroviral-induced immunoreconstitution. We investigated the influence of HIV replication or pro-inflammatory cytokines on lymphopoietic capability of BM-HPCs from 7 viremic (VR) and 5 non-viremic (NVR) HIV infected patients. We found that BM-HPCs from VR patients were unable to differentiate in vitro toward T cells, and produced pro-inflammatory cytokines in the absence of viral replication. In contrast, the lymphoid differentiation potential of BM-HPCs was partially restored after successful antiretroviral therapy. We also showed that TLR8 triggering induced BM-HPCs from healthy donors to release pro-inflammatory cytokines affecting T cells differentiation. These data suggest that in HIV infected patients the lymphopoiesis capability of BM-HPCs may be modulated by a virus-driven autocrine mechanism involving pro-inflammatory cytokines.

  16. Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Ceccaldi, Raphael; Parmar, Kalindi; Mouly, Enguerran; Delord, Marc; Kim, Jung Min; Regairaz, Marie; Pla, Marika; Vasquez, Nadia; Zhang, Qing-Shuo; Pondarre, Corinne; Peffault de Latour, Régis; Gluckman, Eliane; Cavazzana-Calvo, Marina; Leblanc, Thierry; Larghero, Jérôme; Grompe, Markus; Socié, Gérard; D'Andrea, Alan D; Soulier, Jean

    2012-07-01

    Fanconi anemia (FA) is an inherited DNA repair deficiency syndrome. FA patients undergo progressive bone marrow failure (BMF) during childhood, which frequently requires allogeneic hematopoietic stem cell transplantation. The pathogenesis of this BMF has been elusive to date. Here we found that FA patients exhibit a profound defect in hematopoietic stem and progenitor cells (HSPCs) that is present before the onset of clinical BMF. In response to replicative stress and unresolved DNA damage, p53 is hyperactivated in FA cells and triggers a late p21(Cdkn1a)-dependent G0/G1 cell-cycle arrest. Knockdown of p53 rescued the HSPC defects observed in several in vitro and in vivo models, including human FA or FA-like cells. Taken together, our results identify an exacerbated p53/p21 "physiological" response to cellular stress and DNA damage accumulation as a central mechanism for progressive HSPC elimination in FA patients, and have implications for clinical care.

  17. Resolving Salmonella infection reveals dynamic and persisting changes in murine bone marrow progenitor cell phenotype and function.

    Science.gov (United States)

    Ross, Ewan A; Flores-Langarica, Adriana; Bobat, Saeeda; Coughlan, Ruth E; Marshall, Jennifer L; Hitchcock, Jessica R; Cook, Charlotte N; Carvalho-Gaspar, Manuela M; Mitchell, Andrea M; Clarke, Mary; Garcia, Paloma; Cobbold, Mark; Mitchell, Tim J; Henderson, Ian R; Jones, Nick D; Anderson, Graham; Buckley, Christopher D; Cunningham, Adam F

    2014-08-01

    The generation of immune cells from BM precursors is a carefully regulated process. This is essential to limit the potential for oncogenesis and autoimmunity yet protect against infection. How infection modulates this is unclear. Salmonella can colonize systemic sites including the BM and spleen. This resolving infection has multiple IFN-γ-mediated acute and chronic effects on BM progenitors, and during the first week of infection IFN-γ is produced by myeloid, NK, NKT, CD4(+) T cells, and some lineage-negative cells. After infection, the phenotype of BM progenitors rapidly but reversibly alters, with a peak ∼ 30-fold increase in Sca-1(hi) progenitors and a corresponding loss of Sca-1(lo/int) subsets. Most strikingly, the capacity of donor Sca-1(hi) cells to reconstitute an irradiated host is reduced; the longer donor mice are exposed to infection, and Sca-1(hi) c-kit(int) cells have an increased potential to generate B1a-like cells. Thus, Salmonella can have a prolonged influence on BM progenitor functionality not directly related to bacterial persistence. These results reflect changes observed in leucopoiesis during aging and suggest that BM functionality can be modulated by life-long, periodic exposure to infection. Better understanding of this process could offer novel therapeutic opportunities to modulate BM functionality and promote healthy aging.

  18. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

    Science.gov (United States)

    Zahr, Abdallah Abou; Salama, Mohamed E.; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-01-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen 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 myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  19. Blood and Bone Marrow Donation

    Science.gov (United States)

    ... waiting for a stem cell transplant. 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 ...

  20. Bone marrow edema syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E. [University of Ioannina, Department of Orthopaedic Surgery, School of Medicine, Ioannina (Greece); Karantanas, Apostolos H. [University of Crete School of Medicine, Department of Radiology, Heraklion (Greece)

    2009-05-15

    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.)

  1. A critical role of Src family kinase in SDF-1/CXCR4-mediated bone-marrow progenitor cell recruitment to the ischemic heart.

    Science.gov (United States)

    Cheng, Min; Huang, Kai; Zhou, Junlan; Yan, Dewen; Tang, Yao-Liang; Zhao, Ting C; Miller, Richard J; Kishore, Raj; Losordo, Douglas W; Qin, Gangjian

    2015-04-01

    The G protein-coupled receptor CXCR4 and its ligand stromal-cell derived factor 1 (SDF-1) play a crucial role in directing progenitor cell (PC) homing to ischemic tissue. The Src family protein kinases (SFK) can be activated by, and serve as effectors of, G proteins. In this study we sought to determine whether SFK play a role in SDF-1/CXCR4-mediated PC homing. First, we investigated whether SDF-1/CXCR4 signaling activates SFK. Bone-marrow mononuclear cells (BM MNCs) were isolated from WT and BM-specific CXCR4-KO mice and treated with SDF-1 and/or CXCR4 antagonist AMD3100. SDF-1 treatment rapidly induced phosphorylation (activation) of hematopoietic Src (i.e., Lyn, Fgr, and Hck) in WT cells but not in AMD3100-treated cells or CXCR4-KO cells. Then, we investigated whether SFK are involved in SDF-1/CXCR4-mediated PC chemotaxis. In a combined chemotaxis and endothelial-progenitor-cell (EPC) colony assay, Src inhibitor SU6656 dose-dependently inhibited the SDF-1-induced migration of colony-forming EPCs. Next, we investigated whether SFK play a role in SDF-1/CXCR4-mediated BM PC homing to the ischemic heart. BM MNCs from CXCR4BAC:eGFP reporter mice were i.v. injected into WT and SDF-1BAC:SDF1-RFP transgenic mice following surgically-induced myocardial infarction (MI). eGFP(+) MNCs and eGFP(+)c-kit(+) PCs that were recruited in the infarct border zone in SDF-1BAC:SDF1-RFP recipients were significantly more than that in WT recipients. Treatments of mice with SU6656 significantly reduced eGFP(+) and eGFP(+)c-kit(+) cell recruitment in both WT and SDF-1BAC:RFP recipients and abrogated the difference between the two groups. Remarkably, PCs isolated from BM-specific C-terminal Src kinase (CSK)-KO (Src activated) mice were recruited more efficiently than PCs from WT PCs in the WT recipients. In conclusion, SFK are activated by SDF-1/CXCR4 signaling and play an essential role in SDF-1/CXCR4-mediated BM PC chemotactic response and ischemic cardiac recruitment.

  2. p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

    Directory of Open Access Journals (Sweden)

    Kyung Hee Chang

    2014-12-01

    Full Text Available In the bone marrow (BM, hematopoietic progenitors (HPs reside in specific anatomical niches near osteoblasts (Obs, macrophages (MΦs, and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression, and HP chemotaxis toward Cxcl12, resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by deficiency of the p62 PB1-binding partner Nbr1. A functional “MΦ-Ob niche” is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis, and BM progenitor retention.

  3. 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.

  4. Spine fusion using cell matrix composites enriched in bone marrow-derived cells.

    Science.gov (United States)

    Muschler, George F; Nitto, Hironori; Matsukura, Yoichi; Boehm, Cynthia; Valdevit, Antonio; Kambic, Helen; Davros, William; Powell, Kimerly; Easley, Kirk

    2003-02-01

    Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting.

  5. 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

  6. Autologous bone marrow transplantation by photodynamic therapy

    Science.gov (United States)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  7. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  8. Bone Marrow Transplants: "Another Possibility at Life"

    Science.gov (United States)

    ... page please turn Javascript on. Feature: Bone Marrow Transplants “Another Possibility at Life” Past Issues / Summer 2011 ... for 16,000 of them, a bone marrow transplant is the best treatment option, notes Susan F. ...

  9. 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...

  10. Comportamento biológico de matriz scaffold acrescida de células progenitoras na reparação óssea Bone marrow progenitor cells enriched scaffold biological behavior in bone repair

    Directory of Open Access Journals (Sweden)

    Débora Cristina Olsson

    2008-11-01

    synthetic and natural scaffolds. To pursue these objectives, specific combinations of autologous or alogenous bone marrow progenitor cells seeded over a three-dimension scaffold with adequate properties, creating a hybrid material that can be modulated to patient reinsertion. In this review, information about synthetic and natural biological materials indicated to bone grats, combined or not with progenitor cells, aiming to stimulate bone healing process are presented.

  11. 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…

  12. Properties of immature myeloid progenitors with nitric-oxide-dependent immunosuppressive activity isolated from bone marrow of tumor-free mice.

    Science.gov (United States)

    Forghani, Parvin; Harris, Wayne; Giver, Cynthia R; Mirshafiey, Abbas; Galipeau, Jacques; Waller, Edmund K

    2013-01-01

    Myeloid derived suppressor cells (MDSCs) from tumor-bearing mice are important negative regulators of anti-cancer immune responses, but the role for immature myeloid cells (IMCs) in non-tumor-bearing mice in the regulation of immune responses are poorly described. We studied the immune-suppressive activity of IMCs from the bone marrow (BM) of C57Bl/6 mice and the mechanism(s) by which they inhibit T-cell activation and proliferation. IMCs, isolated from BM by high-speed FACS, inhibited mitogen-induced proliferation of CD4(+) and CD8(+) T-cells in vitro. Cell-to-cell contact of T-cells with viable IMCs was required for suppression. Neither neutralizing antibodies to TGFβ1, nor genetic disruption of indolamine 2,3-dioxygenase, abrogated IMC-mediated suppressive activity. In contrast, suppression of T-cell proliferation was absent in cultures containing IMCs from interferon-γ (IFN-γ) receptor KO mice or T-cells from IFN-γ KO mice (on the C57Bl/6 background). The addition of NO inhibitors to co-cultures of T-cells and IMC significantly reduced the suppressive activity of IMCs. IFN-γ signaling between T-cells and IMCs induced paracrine Nitric Oxide (NO) release in culture, and the degree of inhibition of T-cell proliferation was proportional to NO levels. The suppressive activity of IMCs from the bone marrow of tumor-free mice was comparable with MDSCs from BALB/c bearing mice 4T1 mammary tumors. These results indicate that IMCs have a role in regulating T-cell activation and proliferation in the BM microenvironment.

  13. Properties of immature myeloid progenitors with nitric-oxide-dependent immunosuppressive activity isolated from bone marrow of tumor-free mice.

    Directory of Open Access Journals (Sweden)

    Parvin Forghani

    Full Text Available Myeloid derived suppressor cells (MDSCs from tumor-bearing mice are important negative regulators of anti-cancer immune responses, but the role for immature myeloid cells (IMCs in non-tumor-bearing mice in the regulation of immune responses are poorly described. We studied the immune-suppressive activity of IMCs from the bone marrow (BM of C57Bl/6 mice and the mechanism(s by which they inhibit T-cell activation and proliferation. IMCs, isolated from BM by high-speed FACS, inhibited mitogen-induced proliferation of CD4(+ and CD8(+ T-cells in vitro. Cell-to-cell contact of T-cells with viable IMCs was required for suppression. Neither neutralizing antibodies to TGFβ1, nor genetic disruption of indolamine 2,3-dioxygenase, abrogated IMC-mediated suppressive activity. In contrast, suppression of T-cell proliferation was absent in cultures containing IMCs from interferon-γ (IFN-γ receptor KO mice or T-cells from IFN-γ KO mice (on the C57Bl/6 background. The addition of NO inhibitors to co-cultures of T-cells and IMC significantly reduced the suppressive activity of IMCs. IFN-γ signaling between T-cells and IMCs induced paracrine Nitric Oxide (NO release in culture, and the degree of inhibition of T-cell proliferation was proportional to NO levels. The suppressive activity of IMCs from the bone marrow of tumor-free mice was comparable with MDSCs from BALB/c bearing mice 4T1 mammary tumors. These results indicate that IMCs have a role in regulating T-cell activation and proliferation in the BM microenvironment.

  14. Estradiol increases hematopoietic stem and progenitor cells independent of its actions on bone

    NARCIS (Netherlands)

    Illing, Anett; Liu, Peng; Ostermay, Susanne; Schilling, Arndt; de Haan, Gerald; Krust, Andree; Amling, Michael; Chambon, Pierre; Schinke, Thorsten; Tuckermann, Jan P.

    2012-01-01

    Hematopoietic stem and progenitor cells reside in vascular and endosteal niches in the bone marrow. Factors affecting bone remodeling were reported to influence numbers and mobilization of hematopoietic stem cells. We therefore analyzed the effects of estradiol acting anabolic on bone integrity. Her

  15. Bone marrow edema in sports: General concepts

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, F.M. [AZ Sint-Maarten Duffel-Mechelen, Department of Radiology, Rooienberg 25, B-2570 Duffel (Belgium) and University Hospital Antwerp, Department of Radiology, Wilrijkstraat 10, B-2650 Edegem (Belgium)]. E-mail: filip.vanhoenacker@telenet.be; Snoeckx, A. [AZ Sint-Maarten Duffel-Mechelen, Department of Radiology, Rooienberg 25, B-2570 Duffel (Belgium); University Hospital Antwerp, Department of Radiology, Wilrijkstraat 10, B-2650 Edegem (Belgium)

    2007-04-15

    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.

  16. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant.

    Science.gov (United States)

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-05-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

  17. Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow.

    Science.gov (United States)

    Klein, Caroline; Strobel, Julian; Zingsem, Jürgen; Richter, Richard H; Goecke, Tamme W; Beckmann, Matthias W; Eckstein, Reinhold; Weisbach, Volker

    2013-12-01

    In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a single cord blood (CB) unit is not sufficient for allogenic transplantation of adults. Therefore, two CB units are usually required. The ex vivo expansion of HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an alternative. It was investigated, whether bone marrow-derived MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be isolated from placental tissue which is readily available when CB is sampled. In a two-step ex vivo coculture mononuclear cells from cryopreserved CB were cultured with different MSC-feederlayers in a medium supplemented with cytokines (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating factor). Expansion rates were analyzed as well, by long-term culture-initiating cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and CD45(+)-cells. Due to the comparably low number of 5×10(2) to 1×10(4) CD34(+)-cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from 80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. Expansion of LTC-IC was partly observed. Compared to the literature, we found a better expansion rate of CD34(+)-cells with MSCs from all different sources. This is probably due to the comparably low number of 5×10(2) to 1×10 CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was significantly more effective with MSCs from bone marrow compared to MSCs from amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow with MSCs from CB and

  18. 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.

  19. Stem and progenitor cells: advancing bone tissue engineering.

    Science.gov (United States)

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  20. 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.

  1. Bone marrow-derived cells are present in Mooren's ulcer.

    Science.gov (United States)

    Ye, Juan; Chen, Jian; Kim, Jae Chan; Yao, Ke

    2004-01-01

    To investigate whether bone marrow-derived cells are present in Mooren's ulcer and involved in its destructive and regenerative disease course, tissue specimens were collected from 3 eyes of 3 patients with Mooren's ulcer that underwent lamellar keratectomy. Three normal donor limbal corneoscleras served as controls. Immunohistochemical staining patterns were analyzed by using the following antibodies: CD34 (a marker of hematopoietic progenitor cells and endothelium), c-kit (a marker of hematopoietic and stromal progenitor cells) and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhematopoietic progenitor cells). Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stromal cells were seen in normal limbal cornea, but no immunoreactivity for c-kit and STRO-1 was found. Bone marrow-derived cells are present in Mooren's ulcer and contribute to its destructive and regeneration process by synergizing with other factors. Specific therapeutic strategies that target the role of these cells in Mooren's ulcer are anticipated.

  2. Radionuclide imaging of bone marrow disorders

    NARCIS (Netherlands)

    Agool, Ali; Glaudemans, Andor W. J. M.; Boersma, Hendrikus H.; Dierckx, Rudi A. J. O.; Vellenga, Edo; Slart, Riemer H. J. A.

    2011-01-01

    Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-label

  3. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    Science.gov (United States)

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    hair. The viability of the compact bone, bone marrow and skin at 100 days posttransplant was confirmed by histologic evaluation, and bone marrow revealed active hematopoiesis. Bilateral skin/bone transplantation model may serve as an experimental tool to study new strategies in tolerance induction by altering the amount of the immunogenic load in the form of skin transplant and bone marrow delivery in the vascularized form, allowing for expedited engraftment of stem and progenitor cells.

  4. 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.

  5. Soluble factor cross-talk between human bone marrow-derived hematopoietic and mesenchymal cells enhances in vitro CFU-F and CFU-O growth and reveals heterogeneity in the mesenchymal progenitor cell compartment.

    Science.gov (United States)

    Baksh, Dolores; Davies, John E; Zandstra, Peter W

    2005-11-01

    The homeostatic adult bone marrow (BM) is a complex tissue wherein physical and biochemical interactions serve to maintain a balance between the hematopoietic and nonhematopoietic compartments. To focus on soluble factor interactions occurring between mesenchymal and hematopoietic cells, a serum-free adhesion-independent culture system was developed that allows manipulation of the growth of both mesenchymal and hematopoietic human BM-derived progenitors and the balance between these compartments. Factorial experiments demonstrated a role for stem cell factor (SCF) and interleukin 3 (IL-3) in the concomitant growth of hematopoietic (CD45+) and nonhematopoietic (CD45-) cells, as well as their derivatives. Kinetic tracking of IL-3alpha receptor (CD123) and SCF receptor (CD117) expression on a sorted CD45- cell population revealed the emergence of CD45-CD123+ cells capable of osteogenesis. Of the total fibroblast colony-forming units (CFU-Fs) and osteoblast colony-forming units (CFU-O), approximately 24% of CFU-Fs and about 22% of CFU-Os were recovered from this population. Cell-sorting experiments demonstrated that the CD45+ cell population secreted soluble factors that positively affect the survival and proliferation of CFU-Fs and CFU-Os generated from the CD45- cells. Together, our results provide insight into the intercellular cytokine network between hematopoietic and mesenchymal cells and provide a strategy to mutually culture both mesenchymal and hematopoietic cells in a defined scalable bioprocess.

  6. Progenitor cells trapped in marrow filters can reduce GvHD and transplant mortality.

    Science.gov (United States)

    Vicente, D; Podestà, M; Pitto, A; Pozzi, S; Lucchetti, S; Lamparelli, T; Tedone, E; Ibatici, A; Figari, O; Frassoni, F; Van Lint, M T; Piaggio, G; Sacchi, N; Bacigalupo, A

    2006-07-01

    A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001-2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997-2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II-IV graft-versus-host disease (GvHD) (42 vs 15%, P=0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P=0.04). The actuarial survival at 5 years is 69 vs 87%, respectively (P=0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.

  7. Bone marrow examination in pancytopenia.

    Science.gov (United States)

    Rangaswamy, M; Prabhu; Nandini, N M; Manjunath, G V

    2012-08-01

    Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.

  8. Therapy Effect: Impact on Bone Marrow Morphology.

    Science.gov (United States)

    Li, K David; Salama, Mohamed E

    2016-03-01

    This article highlights the most common morphologic features identified in the bone marrow after chemotherapy for hematologic malignancies, growth-stimulating agents, and specific targeted therapies. The key is to be aware of these changes while reviewing post-therapeutic bone marrow biopsies and to not mistake reactive patterns for neoplastic processes. In addition, given the development and prevalent use of targeted therapy, such as tyrosine kinase inhibitors and immune modulators, knowledge of drug-specific morphologic changes is required for proper bone marrow interpretation and diagnosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mikosch, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Zitter, F. [Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Gallowitsch, H.J.; Lind, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Wuertz, F. [Dept. of Pathology, State Hospital Klagenfurt (Austria); Mehta, A.B.; Hughes, D.A. [Lysosomal Storage Disorder Unit, Dept. of Academic Haematology, Royal Free and Univ. Coll. Medical School, London (United Kingdom)

    2008-07-01

    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.

  10. Effect of bone marrow mesenchymal stem cells on the proliferation of bone marrow CD34~+ cells in vitro

    Institute of Scientific and Technical Information of China (English)

    王荣

    2013-01-01

    Objective To investigate the effect on the marrow CD34+ cells by bone marrow mesenchymal stem cells(BMMSC),VarioMACS was used to sort bone marrow CD34+ cells,and then the purity of CD34+ cell was tested by FCM. Marrow mononuclear cells from abortion fetal bone marrow were isolated,and BMMSC were

  11. Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells

    NARCIS (Netherlands)

    Mendes, SC; Tibbe, JM; Veenhof, M; Both, S; Oner, FC; van Blitterswijk, CA; de Bruijn, Joost D.

    2004-01-01

    The use of cell therapies in bone reconstruction has been the subject of extensive research. It is known that human bone marrow stromal cell (HBMSC) cultures contain a population of progenitor cells capable of differentiation towards the osteogenic lineage. In the present study, the correlation betw

  12. 大鼠多能成体祖细胞体外成软骨的诱导和鉴定%Chondrogenesis of Rats’Bone Marrow-derived Multipotent Adult Progenitor Cells in vitro and Related Identification

    Institute of Scientific and Technical Information of China (English)

    徐海艇; 潘骏; 李永领; 朱烈烈

    2016-01-01

    [Objective] To explore chondrogenic differentiation of rats bone marrow-derived multipotent adult progenitor cells(MAPCs) in experimental culture medium.[Methods] MAPCs were isolated from rats bone marrow and expanded to passage 2. The morphology of MAPCs was observed in vitro. Then the cell groups were cultured in chondrogenic media of H-DMEM containing TGF-β3, BMP-6, IGF-1, the control one was made natural differentiation with routine fluid 10% FB5, and dexamethasone forming cell pellet and assessed by Safranin O and collagen Ⅱ staining. And Alcian blue chromatomery of glycosaminoglycan(GAG) was used to determine the differentiation. [Results] MAPCs demonstrated fibroblast-like morphology and showed good proliferation ability. After chondrogenic induction for 4 weeks, the pellets formed by MAPCs had a transparent white cartilage-like morphology in chondrogenic medium while a less shape in control medium. Histologically, the group showed a homogeneous cartilage-like structure with strong safranin O staining and strong collagen 2 staining. Alcian blue staining showed the content of GAG formatting were higher than the control group(P<0.05), with difference of statistical meaning. [Conclusion]MAPCs have high chondrogenic potential and could be an ideal seed in cartilage tissue engineering.%[目的]探讨大鼠多能成体祖细胞(multipotent adult progenitor cells,MAPCs)在特定培养条件下向软骨细胞定向分化的能力。[方法]分离培养大鼠MAPCs,扩增至第2代,观察其形态学特点,并将其离心成团后分为2组,诱导组应用转化生长因子-β3(transforming growth factor-β3,TGF-β3)、骨形态发生蛋白-6(bone morphogenetic protein-6,BMP-6)、胰岛素样生长因子-1(insulin-like growth factors-1,IGF-1)及地塞米松等进行成软骨诱导分化,对照组用含10%胎牛血清(fetal bovine serum, FBS)的高糖DMEM培养液(dulbecco's modifiedeagle medium high-glucose, H-DMEM)常规

  13. Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

    OpenAIRE

    2010-01-01

    The bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMC) transplantation (BMT) may be of assistance in achieving tissue repair and regeneration, as well as in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMC to preserve functiona...

  14. Selective retention of bone marrow-derived cells to enhance spinal fusion.

    Science.gov (United States)

    Muschler, George F; Matsukura, Yoichi; Nitto, Hironori; Boehm, Cynthia A; Valdevit, Antonio D; Kambic, Helen E; Davros, William J; Easley, Kirk A; Powell, Kimerly A

    2005-03-01

    Connective tissue progenitors can be concentrated rapidly from fresh bone marrow aspirates using some porous matrices as a surface for cell attachment and selective retention, and for creating a cellular graft that is enriched with respect to the number of progenitor cells. We evaluated the potential value of this method using demineralized cortical bone powder as the matrix. Matrix alone, matrix plus marrow, and matrix enriched with marrow cells were compared in an established canine spinal fusion model. Fusions were compared based on union score, fusion mass, fusion volume, and by mechanical testing. Enriched matrix grafts delivered a mean of 2.3 times more cells and approximately 5.6 times more progenitors than matrix mixed with bone marrow. The union score with enriched matrix was superior to matrix alone and matrix plus marrow. Fusion volume and fusion area also were greater with the enriched matrix. These data suggest that the strategy of selective retention provides a rapid, simple, and effective method for concentration and delivery of marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting procedures in various clinical settings.

  15. 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...... 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...

  16. Large-scale gene expression profiling data of bone marrow stromal cells from osteoarthritic donors.

    Science.gov (United States)

    Stiehler, Maik; Rauh, Juliane; Bünger, Cody; Jacobi, Angela; Vater, Corina; Schildberg, Theresa; Liebers, Cornelia; Günther, Klaus-Peter; Bretschneider, Henriette

    2016-09-01

    This data article contains data related to the research article entitled, "in vitro characterization of bone marrow stromal cells from osteoarthritic donors" [1]. Osteoarthritis (OA) represents the main indication for total joint arthroplasty and is one of the most frequent degenerative joint disorders. However, the exact etiology of OA remains unknown. Bone marrow stromal cells (BMSCs) can be easily isolated from bone marrow aspirates and provide an excellent source of progenitor cells. The data shows the identification of pivotal genes and pathways involved in osteoarthritis by comparing gene expression patterns of BMSCs from osteoarthritic versus healthy donors using an array-based approach.

  17. 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.

  18. National Marrow Donor Program. HLA Typing for Bone Marrow Transplantation

    Science.gov (United States)

    2014-11-30

    M, Battiwalla M, Baxter-Lowe LA, Bitan M, Fernandez-Viña M, Gandhi M, Jakubowski AA, Maiers M, Marino SR, Marsh SG, Oudshoorn M, Palmer J, Prasad...1487-1496, 2012 Oct 18. (Response to Letter to the Editor) Peripheral-blood versus bone marrow stem cells. N Engl J Med 368(3):288, 2013 Jan 17. New

  19. Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis.

    Science.gov (United States)

    Ge, Chunxi; Wang, Zhengyan; Zhao, Guisheng; Li, Binbin; Liao, Jinhui; Sun, Hanshi; Franceschi, Renny T

    2016-12-01

    Cell-extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis. Smallie mice (Ddr2(slie/slie) ), which contain a nonfunctional Ddr2 allele, have multiple skeletal defects. A progressive decrease in tibial trabecular bone volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2(wt/slie) , and Ddr2(slie/slie) mice were compared. These changes were associated with reduced trabecular number (Tb.N) and trabecular thickness (Tb.Th) and increased trabecular spacing (Tb.Sp) in both males and females, but reduced cortical thickness only in Ddr2(slie/slie) females. Bone changes were attributed to decreased bone formation rather than increased osteoclast activity. Significantly, marrow fat and adipocyte-specific mRNA expression were significantly elevated in Ddr2(slie/slie) animals. Additional skeletal defects include widened calvarial sutures and reduced vertebral trabecular bone. To examine the role of DDR2 signaling in cell differentiation, bone marrow stromal cells (BMSCs) were grown under osteogenic and adipogenic conditions. Ddr2(slie/slie) cells exhibited defective osteoblast differentiation and accelerated adipogenesis. Changes in differentiation were related to activity of runt-related transcription factor 2 (RUNX2) and PPARγ, transcription factors that are both controlled by MAPK-dependent phosphorylation. Specifically, the defective osteoblast differentiation in calvarial cells from Ddr2(slie/slie) mice was associated with reduced ERK/MAP kinase and RUNX2-S319 phosphorylation and could

  20. Bone marrow transplantation. [Mice, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Storb, R.; Santos, G.W.

    1979-03-01

    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.

  1. Bone Marrow Transplantation in Thalassemia (Part 2

    Directory of Open Access Journals (Sweden)

    Maryam Zakerinia

    2009-06-01

    Full Text Available During the last two decades conventional therapy has improvedthe prognosis of thalassemia. However, despite such improvementit still remains a progressive disease with treatment-relatedcomplications such as hepatitis, liver fibrosis, and cardiac disease.Bone marrow transplantation (BMT can prevent or delayprogression of the aforementioned complications. The importanceof clinical research in the field of BMT was recognizedwith the award of the 1990 Nobel Prize in Physiology andMedicine to E. Donnall Thomas, one of the pioneers of BMT inhumans. George Mathe' was a pioneer in the early developmentof clinical BMT. Mathe' and co-workers were the first to describegraft-versus-host-disease and its treatment, and the graftversus-leukemia effect in human. The first BMT for β-thalassemia major was performed successfully by Thomas andcolleagues in Seattle, in 1981. In the same year another patientwith β-thalassemia major underwent BMT in Pesaro, Italy, byLucarelli and others Since then, several hundred transplantationshave been performed worldwide, mostly in Italy. From 1991through 2007 BMT have been performed on 497 (Tehran=342,Shiraz=155 blood transfusion dependent patients with thalassemiamajor in Iran, with disease-free survival of 71-77% respectively.Because of high graft failure and high rates of graftversus-host-disease rates, BMT from alternative donors shouldbe restricted to patients who have poor life expectancies becausethey cannot receive adequate conventional treatment or becauseof alloimmunization to minor blood antigens. Beginning in theearly 1980s, it was shown that umbilical cord blood containedhigh levels of hematopoietic progenitor cells.

  2. Bone marrow cells and myocardial regeneration.

    Science.gov (United States)

    Wang, Fu-Sheng; Trester, Cathy

    2004-05-01

    Hematopoietic stem cell (HSC) plasticity and its clinical application have been studied profoundly in the past few years. Recent investigations indicate that HSC and other bone marrow stem cells can develop into other tissues. Because of the high morbidity and mortality of myocardial infarction and other heart disorders, myocardial regeneration is a good example of the clinical application of HSC plasticity in regenerative medicine. Preclinical studies in animals suggest that the use of this kind of treatment can reconstruct heart blood vessels, muscle, and function. Some clinical study results have been reported in the past 2 years. In 2003, reports of myocardial regeneration treatment increased significantly. Other studies include observations on the cell surface markers of transplanted cells and treatment efficacy. Some investigations, such as HSC testing, have focused on clinical applications using HSC plasticity and bone marrow transplantation to treat different types of disorders. In this review, we focus on the clinical application of bone marrow cells for myocardial regeneration.

  3. Shifting bone marrow edema of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Moosikasuwan, Josh B.; Schultz, Elizabeth [Department of Radiology, North Shore University Hospital, 300 Community Drive, NY 11030, Manhasset (United States); Miller, Theodore T. [Department of Radiology, North Shore University Hospital, 300 Community Drive, NY 11030, Manhasset (United States); Department of Radiology, North Shore University Hospital, 825 Northern Boulevard, NY 11021, Great Neck (United States); Math, Kevin [Department of Radiology, Beth Israel Medical Center, First Avenue at 16th Street, NY 10003, New York (United States)

    2004-07-01

    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. Diffusion and perfusion imaging of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Biffar, Andreas; Dietrich, Olaf [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Sourbron, Steven [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Division of Medical Physics, University of Leeds, Leeds (United Kingdom); Duerr, Hans-Roland [Department of Orthopedic Surgery, LMU University Hospitals, Grosshadern-Munich (Germany); Reiser, Maximilian F. [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Baur-Melnyk, Andrea, E-mail: andrea.baur@med.uni-muenchen.de [Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany)

    2010-12-15

    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.

  5. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, M; Harmsen, MC; Koerts, JA; Petersen, AH; van Luyn, MJA; Navis, G; Popa, ER

    2005-01-01

    Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned

  6. 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.

  7. Transplantation of bone marrow multipotent adult progenitor cells for treating Parkinson disease in rats%骨髓基质多能成体祖细胞移植治疗大鼠帕金森病

    Institute of Scientific and Technical Information of China (English)

    周瑞祥; 孙圣刚

    2007-01-01

    various characteristics of bone marrow derived-multipotent adult progenitor cells (MAPCs) enable them to become one the ideal sources of cells for cell transplantation.OBJECTIVE: To explore the hypothesis that MAPCs were able to enter the brain and reduce the neurological functional deficits in rats by injecting intravenously.DESTGN: A randomized controlled experiment.ETTING: Department of Neurology, Wuhan First Hospital.MATERIALS: The experiments were performed in the laboratory of Department of Neurology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from October 2003 to March 2005. Eighty healthy Sprague-Dawley (SD) rats of 180-200 g were provided by the experimental animal center of Tongji Medical College,Huazhong University of Science and Technology.METHODS: The rats were made into models of Parkinson disease, the bone marrow-derived MAPCs, which were in vitro purified, proliferated and treated with 5-bromo-2-deoxyuridine (BrdU), were injected via caudal vein. After three months,the immunohistochemical technique, reverse transcription-polymerase chain reaction (RT-PCR), electron microscopy and behavioral tests were used to identify the MAPCs or neuron-like cells derived from MAPCs in brain and their functions.MAIN OUTCOME MEASURES: ① Results of behavioral observation; ② Results of immunihistochemical staining.RESULTS: After implantation, MAPCs could survive and differentiate into neuron-like cells in substantia nigra and striatum. MAPCs-derived dopaminergic neurons caused gradual and sustained behavioral restoration of 6-hydroxydopamine (6-OHDA)-mediated motor asymmetry. The levels of dopamine beta-hydroxylase (DBH), nerve growth factor (NGF) or dopamine transporter (DAT) mRNA were up-regulated significantly. It was observed under electron microscope that immature synapse implicated MAPCs- derived neuron should play an important role in the reconstruction of neural circuitry.CONCLUSION: Transplanted bone marrow derived

  8. Early and Late Endothelial Progenitor Cells Derived from Rabbit Bone Marrow Isolated and Cultured by An Improved Method%改良法分离培养兔骨髓源性早晚期内皮祖细胞

    Institute of Scientific and Technical Information of China (English)

    王佐; 张凯; 王仁; 苏维; 李爽; 杨简; 姜志胜

    2011-01-01

    目的 探索简单有效分离培养兔骨髓源性内皮祖细胞的方法,并比较两种内皮祖细胞生物学性状.方法 4周龄左右的新西兰兔,于每侧胫骨取骨髓2mL,密度梯度离心后取单个核细胞接种于培养瓶,48h后将悬浮的细胞收集再次贴壁,血管内皮生长因子诱导其向内皮祖细胞分化.免疫细胞化学鉴定其表面标志物、免疫荧光功能学测定,对比前后两种贴壁细胞生长状况.结果 早期获取的单个核细胞,半小时后就开始贴壁,3天左右即可长出长梭形的细胞,胞体较大,有血岛样克隆形成,随后培养可形成管腔样结构,10天左右即可呈漩涡状融合整个培养瓶,但这种细胞传代能力差,为早期内皮祖细胞;第2次贴壁的晚期细胞于贴壁后呈椭圆形生长,贴壁后5-7天即可出现集落,片状生长,最后呈铺路石样融合,并可连续传至10代以上,为晚期内皮祖细胞.第2次贴壁的内皮祖细胞在分化过程中明显失去CD133+,而CD34+表达有所升高,大部分第1次贴壁内皮祖细胞可以吞噬乙酰化低密度脂蛋白和荆豆凝集素1,第2次贴壁内皮祖细胞功能学鉴定结果与第1次贴壁的结果类似.结论 改良后的密度梯度离心法结合差速贴壁法能有效分离培养兔骨髓源性内皮祖细胞,第2次贴壁的内皮祖细胞生长能力更强.%Aim To establish an available and convenient method to isolate and culture the rabbit bone marrow-derived endothelial progenitor cells (EPC) and compare the characteristics of the two different EPC. Methods Obtained 2 mL bone marrow from each shinbone of about 4 weeks old New Zealand rabbit, mononuclear cells ( MNC) were I-solated by Ficoll density gradient centrifugation method and planted in the first culture flask, after incubated for 48 h, collecting the suspended cells into the second flask, supplemented with vascular endothelial growth factor ( VEGF) in order to induce cells differentiation into EPC. To

  9. Autophagy regulation of rat bone marrow-derived endothelial progenitor cells and cell functions%调控内皮祖细胞自噬促进其功能的实验研究

    Institute of Scientific and Technical Information of China (English)

    胡楠; 钱爱民; 孔令尚; 李承龙; 于小滨; 陈弘; 杜晓龙; 李晓强

    2015-01-01

    Objective To investigate the effect of autophagy regulation of rat bone marrow-derived endothelial progenitor cells (EPCs) on cell functions.Methods EPCs isolated from rat bone marrow were treated with rapamycin (10 μg/L), 3-MA (5 mmol/L) or wortmannin (50 nmol/L) for 24 hours.Cell migration was assayed using a 24-well transwell cell culture chamber.Tube formation was assayed on GFR (growth factor-reduced)-Matrigel.Angiogenic cytokine was analyzed by using corresponding ELISA kits.Expression of the autophagy marker protein LC3-Ⅱ, LAMP2A and HSC70 were analyzed by Western blotting.Results 10 μg/L rapamycin treatment inhibited EPCs migration, tube formation and secretion of angiogenic cytokines.EPCs function significantly increased following 5 mmol/L 3-MA or 50 nmol/L wortmannin treatment.Western blotting showed that rapamycin increased LC3-Ⅱ protein expression, but reduced LAMP2A and HSC70 expression.3-MA or wortmannin treatment reduced LC3-Ⅱ protein expression (P < 0.05), while increased LAMP2A and HSC70 expression.Conclusions Moderate inhibition of autophagy promotes the function of EPCs probably by reducing LC3-Ⅱ protein levels.%目的 研究利用自噬促进剂雷帕霉素和抑制剂3-甲基腺嘌呤(3-methlyadenine,3-MA)或渥曼青霉素调控内皮祖细胞(endothelial progenitor cells,EPCs)自噬,观察对其迁移、成血管和分泌能力的影响以及微管相关蛋白1轻链3-Ⅱ(microtubule-associated protein 1 light chain3-Ⅱ,LC3-Ⅱ)、溶酶体相关膜蛋白2A(lysosome-associated membrane proteintype 2A,LAMP2A)和热休克蛋白70(heatshock protein 70,HSC70)的水平变化.方法 密度梯度离心法分离SD大鼠的骨髓单个核细胞,EGM-2MV培养基诱导、培养、扩增骨髓源性EPCs.分为四组,即雷帕霉素组,3-MA组,渥曼青霉素组和对照组,分别用10μg,/L雷帕霉素,5 mmol/L 3-MA,50 nmol/L渥曼青霉素处理EPCs 12 h,对照组加入等量培养基.分别用transwell实验及成血管实验检测EPCs迁

  10. 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.

  11. Pain and Anxiety During Bone Marrow Biopsy

    NARCIS (Netherlands)

    Tanasale, Betty; Kits, Jenne; Kluin, Philip M.; Trip, Albert; Kluin-Nelemans, Hanneke C.

    2013-01-01

    A bone marrow biopsy is considered to be painful, often causing anxiety. We observed large differences between patients and wondered which factors cause pain and anxiety. In a prospective study, 202 patients were analyzed. Experienced hematologists and fellows in training (17% of biopsies) performed

  12. The bone marrow endosteal niche: how far from the surface?

    Science.gov (United States)

    Cordeiro-Spinetti, Eric; Taichman, Russell S; Balduino, Alex

    2015-01-01

    Hematopoietic stem cells (HSC) self-renewal takes place in the same microenvironment in which massive hematopoietic progenitor proliferation, commitment, and differentiation will occur. This is only made possible if the bone marrow microenvironment comprises different specific niches, composed by different stromal cells that work in harmony to regulate all the steps of the hematopoiesis cascade. Histological and functional assays indicated that HSC and multipotent progenitors preferentially colonize the endosteal and subendosteal regions, in close association with the bone surface. Conversely, committed progenitors and differentiated cells are distributed in the central and perisinusoidal regions, respectively. Over the last decade, many investigative teams sought to define which cell types regulate the HSC niche, how they are organized, and to what extent they interface with each other. System dynamics requires different stromal cells to operate distinct functions over similar HSC pools rather than a single stromal cell type controlling everything. Therefore, our focus herein is to depict the players in the endosteal and subendosteal regions, named the endosteal niche, a necessary step to better understand the interactions of the HSC within the niche and to identify potential targets to manipulate and/or modulate normal and malignant HSC behavior.

  13. Bone marrow scan evaluation of arthropathy in sickle cell disorders

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, A.; Schumacher, H.R.; Dorwart, B.; Kuhl, D.E.

    1976-04-01

    Twelve patients with sickle cell hemoglobinopathies and arthropathy were studied, using technetium Tc 99m sulfur colloid bone marrow scans. Eight of 12 had decreased marrow radionuclide activity adjacent to painful joints, suggesting obliteration of vessels supplying bone marrow. Four patients without marrow defects on scanning had causes other than infarction for their joint symptoms, viz, small fractures, postinfectious synovitis, degenerative arthritis, and osteochondromas. Roentgenograms never showed bony abnormalities in five patients with marrow infarctions, and, in three others, showed defects several months later than did the marrow scans. Bone marrow scans offer a sensitive and early diagnostic aid in sickle cell hemoglobinopathies with arthropathy.

  14. Biomarkers of bone and mineral metabolism following bone marrow transplantation.

    Science.gov (United States)

    Baek, Ki Hyun; Kang, Moo Il

    2009-01-01

    The loss of bone mass often occurs after patients undergo bone marrow transplantation (BMT). The rapid impairment of bone formation and the increase in bone resorption, as mirrored by the biochemical markers of bone turnover, might play a role in this bone loss, and especially during the immediate post-BMT period. The possible direct causes for this paradoxical uncoupling are exposure to immunosuppressants, hypogonadism, the changes of cytokines, the changes of the bone growth factors, and the damage to the osteoprogenitor cells because of myeloablative therapy. In this chapter, we discuss the general aspects of post-BMT bone loss with a peculiar focus on the remodeling imbalance of bone and its relation to the use of immunosuppressants and the changes of sex hormones, growth factors, and cytokines.

  15. Bone-Marrow-Derived Mesenchymal Stem Cells for Organ Repair

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM, umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair.

  16. Bone marrow: its contribution to heme catabolism.

    Science.gov (United States)

    Mähönen, Y; Anttinen, M; Vuopio, P; Tenhunen, R

    1976-01-01

    Heme oxygenase (HO) and biliverdin reductase (BR), the two NADPH-dependent enzymes involved in the degradation of hemoglobin and its derivatives, were measured in bone marrow aspirates from 5 hematologically normal persons, 4 patients with chronic leucemia (CL), 11 patients with acute leucemia (AL), 8 patients with refractory sideroblastic anemia (RA), 7 patients with iron-deficiency anemia (IA), 5 patients with hemolytic anemia (HA), and 7 patients with secondary anemia (SA) to determine the enzymatic capacity of the bone marrow in different hematologic disorders for heme catabolism. HO activity in the bone marrow of normal persons was 0.42 +/- 0.28 (SD) nmoles bilirubin/10 mg protein/min; in CL, 2.15 +/- 1.34; in AL, 0.39 +/- 0.25; in RA, 0.58 +/- 0.37; in IA, 0.41 +/- 0.28; in HA, 2.56 +/- 1.40; and in SA, 1.72 +/- 1.06. BR activity, respectively, was in normal persons 8.7 +/- 2.4 (SD) nmoles bilirubin/10 mg protein/min; in CL, 13.6 +/- 9.1; in AL, 3.8 +/- 3.1 in RA, 5.1 +/- 2.7; in IA, 5.5 +/- 3.7; in HA, 17.0 +/- 7.2; and in SA, 10.5 +/- 4.2. On the basis of these findings it seems evident that both oxygenase and biliverdin reductase activities of the bone marrow are capable of adaptive regulation. The physiologic role of bone marrow in heme catabolism seems to be of significant importance.

  17. Effects of Ligustrazine on Expression of Bone Marrow Heparan Sulfates in Syngeneic Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    任天华; 刘文励; 孙汉英; 戴琪琳; 孙岚

    2003-01-01

    To explore the effects of ligustrazine on bone marrow heparan sulfates (HS) expression in bone marrow transplantation (BMT) mice, the syngeneic BMT mice were orally given 2 mg ligustrazine twice a day. On the 7th, 10th, 14th, 18th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the expression levels of HS in bone marrow and on the stromal cell surfaces were detected by immunohistochemistry and flow cytometry assay respectively. In ligustrazine-treated group, the white blood cells (WBC) and BMNC on the 7th, 10th, 14th, 18th day and platelets (PLT) on the 7th, 10th day were all significantly more than those in control group (P<0.05). The bone marrow HS expression levels in ligustrazine-treated group were higher than those in control group (P<0. 05) on the 7th, 10th, 14th, 18th day. However, the HS expression levels on the stromal cell surfaces showed no significant difference between the two groups on the 18th day (P>0. 05). It was concluded that ligustrazine could up-regulate HS expression in bone marrow, which might be one of the mechanisms contributing to ligustrazine promoting hematopoietic reconstitution after BMT.

  18. Bone marrow cells differentiation into organ cells using stem cell therapy.

    Science.gov (United States)

    Yang, Y-J; Li, X-L; Xue, Y; Zhang, C-X; Wang, Y; Hu, X; Dai, Q

    2016-07-01

    Bone marrow cells (BMC) are progenitors of bone, cartilage, skeletal tissue, the hematopoiesis-supporting stroma and adipocyte cells. BMCs have the potential to differentiate into neural cells, cardiac myocytes, liver hepatocytes, chondrocytes, renal, corneal, blood, and myogenic cells. The bone marrow cell cultures from stromal and mesenchymal cells are called multipotent adult progenitor cells (MAPCs). MAPCs can differentiate into mesenchymal cells, visceral mesoderm, neuroectoderm and endoderm in vitro. It has been shown that the stem cells derived from bone marrow cells (BMCs) can regenerate cardiac myocytes after myocardial infarction (MI). Adult bone marrow mesenchymal stem cells have the ability to regenerate neural cells. Neural stem/progenitor cells (NS/PC) are ideal for treating central nervous system (CNS) diseases, such as Alzheimer's, Parkinson's and Huntington disease. However, there are important ethical issues about the therapeutic use of stem cells. Neurons, cardiac myocytes, hepatocytes, renal cells, blood cells, chondrocytes and adipocytes regeneration from BMCs are very important in disease control. It is known that limbal epithelial stem cells in the cornea can repair the eye sight and remove symptoms of blindness. Stem cell therapy (SCT) is progressing well in animal models, but the use of SCT in human remains to be explored further.

  19. 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....... This enables MRI to detect differences between fatty, fibrotic, aplastic and hypercellular marrow in patients with haematological disease. MRI can evaluate the distribution of bone marrow disease because it has the potential for visualization of almost the entire bone marrow compartment. However, MRI is unable...... to establish the primary diagnosis in haematological bone marrow disease with diffuse hypercellular marrow. In case of insufficient biopsy, MRI can provide important differential diagnostic information as well as guidance for further biopsy attempts. MRI is a useful complement to morphological bone marrow...

  20. Bone marrow micrometastasis detected by flow cytometry is associated bone, bone marrow, lung macrometastasis in breast cancer

    Directory of Open Access Journals (Sweden)

    Mustafa Salih Akin

    2014-04-01

    Material and Methods: Bone marrow samples were obtained from 52 breast cancer patients and 16 control patients via aspiration from the iliac spine at the time of first diagnosis after the surgery. Epithelial cells were identified with anti-cytokeratin monoclonal antibody, and double-staining with propidium iodide and CD45using flow cytometry. Results: In all, 2 (12.5% of the 16 control patients and 11 (21% of the 52 breast cancer patients had cytokeratin-18 positive cells in their bone marrow. A relationship between the presence of occult metastatic cells in bone marrow, and the presence/absence of lymph node metastases, tumor size, stage, menopausal status, hormone receptor status, histological grade, c-erb-B2 expression, tumor subtype, lymphovascular invasion, Ductal carcinoma in situ (DCIS component, and gender was not observed. Significant positive relationships were observed between bone marrow micrometastasis, and age, and bone, bone marrow, lung, and liver metastases. Conclusion: Bone marrow micrometastasis was associated with age, bone, bone marrow, lung, and liver metastases at the time of diagnosis.. [Cukurova Med J 2014; 39(2.000: 305-314

  1. The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis

    Science.gov (United States)

    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 and regulation of BM adipocyte formation are not fully understood. In this review, we will discuss recent findings pertaining to identification and characterization of adipocyte progenitor cells in BM and the regulation of differentiation into mature adipocytes. We have also emphasized the clinical relevance of these findings. PMID:27708616

  2. [Prolonged acute pancreatitis after bone marrow transplantation].

    Science.gov (United States)

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  3. Karyotype of cryopreserved bone marrow cells

    Directory of Open Access Journals (Sweden)

    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.

  4. Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

    Institute of Scientific and Technical Information of China (English)

    Bruno; C; Huber; Ulrich; Grabmaier; Stefan; Brunner

    2014-01-01

    Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.

  5. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  6. Improved method for assessing iron stores in the bone marrow

    NARCIS (Netherlands)

    Phiri, K.S.; Calis, J.C.J.; Kachala, D.; Borgstein, E.; Waluza, J.; Bates, I.; Brabin, B.; Boele van Hensbroek, M.

    2009-01-01

    BACKGROUND: Bone marrow iron microscopy has been the "gold standard" method of assessing iron deficiency. However, the commonly used method of grading marrow iron remains highly subjective. AIM: To improve the bone marrow grading method by developing a detailed protocol that assesses iron in fragmen

  7. Treatment of Bone Marrow Failure Syndrome with Integrated Traditional and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    MA Rou

    2007-01-01

    @@ Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both included in the bone marrow failure syndromes (BMFS). AA is a group of diseases characterized by hematopoietic stem/progenitor cell damage,peripheral blood cytopenia, and clinical manifestations including anemia, bleeding and infection, which eventually lead to bone marrow failure.The incidence rate of AA in China is 7.4/106, higher than that in Western countries, among which the morbidity of acute AA and chronic AA (CAA) is 1.4/106 and 6.0/106,respectively.

  8. Bone Marrow Failure Secondary to Cytokinesis Failure

    Science.gov (United States)

    2015-12-01

    have assessed the role of FA pathway in mitosis and confirmed that murine FA-deficient hematopoietic stem cells exhibit p53- mediated growth defects...results suggest that bone marrow failure in FA may be caused, in part, by p53- mediated cellular defects and underscore the importance of... mediated apoptosis of HSCs due to cytokinesis failure. The major goal of the project was to assess whether the p53- mediated apoptosis due to

  9. Acceleration of Immune Reconstitution after Bone Marrow Transplantation in Mice by Bone Marrow Stromal

    Institute of Scientific and Technical Information of China (English)

    秦凤华; 蒋激扬; 李爱玲; 金永柱; 郝洁; 谢蜀生

    2003-01-01

    To observe potential effect of the engineered bone marrow stromal cell line QXMSC1 secreting IL-6 (QXMSCIL-6) on accelerating immnune reconstitution in syngeneic bone marrow transplantation in mice, QXMSC1 was transfected with the eukaryocytic expression vector pcDNAIL-6, which contained hIL-6 cDNA by liposome-mediated gene transfecting technique. G418-resistance clone was selected by limiting dilution. The highest secreting clone was selected by ELISA assay and used in animal experiments. The recipient mice (BALB/c) were lethally irradiated and cotransplanted syngeneic bone marrow (107/mice) and the QXMSCIIL-6 (5×105/mice). Lymphocyte proliferation induced by ConA and LPS, helper T lymphocyte precursor (HTLp), cytotoxic T lymphocyte precursor (CTLp), plaque-forming cell (PFC), delayed type hypersensitivity (DTH) were examined 30, 60 days in post transplantation respectively. The results showed that lymphocytes proliferation to ConA and LPS, HTLp, CTLp increased, DTH and PFC were improved by cografted stromal cells QXMSCIIL-6 on 30, 60 days after BMT. These results demonstrated that the bone marrow stromal cell line QXMSC1 IL-6 transfected with IL-6 (QXMSC11L-6) accelerated immnune reconstitution in syngeneic bone marrow transplantation.

  10. Tetanus after allogeneic bone-marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S. (Westminster Medical School, London (UK))

    1982-11-13

    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.

  11. Isolation, culture and identification of early and late endothelial progenitor cells from rat bone marrow and peripheral blood★◆%大鼠骨髓和外周血早晚期内皮祖细胞的分离培养和鉴定★◆

    Institute of Scientific and Technical Information of China (English)

    王红娟; 王娟; 李楠; 高航; 刘亢丁

    2013-01-01

      背景:旨在从大鼠外周血及骨髓中提取内皮祖细胞,培养晚期内皮祖细胞,为干细胞移植治疗或通过内皮祖细胞联合基因治疗使内皮祖细胞高表达血管新生诱导因子,达到促进缺血性脑血管病血管新生的目的。目的:从大鼠骨髓及外周血中分离出内皮祖细胞并对其进行鉴定。方法:使用密度梯度离心及贴壁筛选法从大鼠骨髓和外周血中分离获得单个核细胞,进行诱导培养,观察并记录贴壁细胞的生物学特征;选取内皮祖细胞特异性表面标志 CD133、CD34、KDR 对原代细胞进行免疫荧光检测,利用流式细胞学技术检测 KDR、CD34表达,并通过吞噬功能实验进一步鉴定培养细胞。结果与结论:大鼠骨髓和外周血能够分离获得早晚期内皮祖细胞;贴壁细胞免疫荧光检测 CD34、CD133、KDR 表达阳性;流式细胞学检测 CD34、KDR 表达阳性;贴壁细胞能够吞噬 ac-LDL,结合 UEA-1。实验成功从大鼠骨髓及外周血中分离出内皮祖细胞;并获得了增殖活性强的晚期内皮祖细胞,找到了更好的成血管干细胞的种子来源。%BACKGROUND: Our experiments intended to obtain bone marrow endothelial progenitor cells from rat peripheral blood and bone marrow, and culture the late endothelial progenitor cells to perform the stem cells transplantation or endothelial progenitor cells combined with gene therapy in order to highly express the angiogenic factors, thus to promote the angiogenesis after ischemic cerebrovascular disease. OBJECTIVE: To isolate and identify the endothelial progenitor cells from rat bone marrow and peripheral blood. METHODS: Mononuclear cells were obtained by using density gradient centrifugation and adherence screening method from bone marrow and peripheral blood of rats. Then the cells were induced, and the biological characteristics of the adherent cells were observed and recorded. Endothelial

  12. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    Science.gov (United States)

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

  13. Hematopoietic effects of benzene inhalation assessed by long-term bone marrow culture.

    Science.gov (United States)

    Abraham, N G

    1996-12-01

    The strong and long-lasting hematotoxic effect after benzene exposure in vivo (300 ppm, 6 hr/day, 5 days/week for 2 weeks) was assessed in mice with bone marrow cells grown in long-term bone marrow culture (LTBMC). Bone marrow cultures initiated 1 day after the last benzene exposure did not produce adequate numbers of hematopoietic cells over 3 weeks, and, in most cases, no erythroid or myeloid clonogenic cells could be recovered. The adherent cell layer of these cultures had a lowered capacity for supporting in vitro hematopoiesis after the second seeding with normal bone marrow cells compared with control cultures. Two weeks after the last benzene exposure, body weight, hematocrit, bone marrow cellularity, and committed hematopoietic progenitor content (BFU-E and CFU-GM) were regenerated to normal or subnormal values, whereas hematopoiesis in LTBMC was very poor. Over 8 weeks, little or no significant committed progenitor production was observed. Treatment of mice exposed to benzene with hemin (three doses of 3 micrograms/g bw i.v. over 2 weeks for a total dose of 9 micrograms/g) partially overcame the toxic effect of benzene on the hematopoietic system as measured by the LTBMC method. Cultures from mice treated with hemin had a modest recovery of BFU-E and CFU-GM clonogenic potential after 5 to 6 weeks in LTBMC. In contrast, little or no recovery was obtained for the adherent cell layer clonogenic capacity, even after hemin treatment. These results clearly indicate a strong, long-lasting toxic effect on the bone marrow stroma and a limited recovery of hematopoietic potential by clonogenic cells of the nonadherent population after in vivo hemin treatment.

  14. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    Science.gov (United States)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early

  15. 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.

  16. A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

    Science.gov (United States)

    Ono, Noriaki; Ono, Wanida; Nagasawa, Takashi; Kronenberg, Henry M

    2014-12-01

    The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals.

  17. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  18. Effects of Ligustrazine on Hematopoiesis in the Early Phase of Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    周银莉; 刘文励; 孙汉英; 徐惠珍; 路武; 孙岚; 孟凡凯

    2002-01-01

    Summary: To investigate the effects of Ligustrazine on histogenesis of bone marrow in the early phase of hematopoietic reconstruction in bone marrow transplantation (BMT) mice. The syngeneic BMT mice model was established. The syngeneic BMT mice were orally given 2 mg Ligustrazine twice a day. 1, 3, 5, 7, 10, 15 and 21 day(s) after BMT, peripheral blood granulocytes and bone marrow nucleated cells (BMNC) were counted and the diameter of central vein and the area of micro-vessel in femur were measured. The effect of Ligustrazine on hematopoietic stem cells was observed by colony forming unit of spleen (CFU-S). The effect of Ligustrazine on hemopoietic progenitors was studied by observing the number of progenitors of Granulocytes/Macrophage on day 10 and day 20 after BMT. In Ligustrazine-treated group, the diameter of center veins and the area of micro-vessel of femur were all significantly less than the control group 7, 10, 15, 21 days after BMT (P<0. 01). In addition, Ligustrazine significantly increased the number of CFU-S on day 10and the number of CFU-GM on day 10, 20 after BMT. These results indicate that Ligustrazine can accelerate the histogenesis of hemopoietic bone marrow, which may be one mechanism by which Ligustrazine promotes hematopoietic reconstitution after BMT.

  19. Bone marrow-derived dendritic cells.

    Science.gov (United States)

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

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

    Science.gov (United States)

    Gessmann, Jan; Köller, Manfred; Godry, Holger; Schildhauer, Thomas Armin; Seybold, Dominik

    2012-01-01

    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.

  1. Bone Formation by Sheep Stem Cells in an Ectopic Mouse Model: Comparison of Adipose and Bone Marrow Derived Cells and Identification of Donor-Derived Bone by Antibody Staining

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Dreyer, Chris Halling; Ditzel, Nicholas;

    2016-01-01

    Background. Scaffolds for bone tissue engineering (BTE) can be loaded with stem and progenitor cells (SPC) from different sources to improve osteogenesis. SPC can be found in bone marrow, adipose tissue, and other tissues. Little is known about osteogenic potential of adipose-derived culture...

  2. Fibrillin-1 microfibrils influence adult bone marrow hematopoiesis.

    Science.gov (United States)

    Smaldone, Silvia; Bigarella, Carolina L; Del Solar, Maria; Ghaffari, Saghi; Ramirez, Francesco

    2016-01-01

    We have recently demonstrated that fibrillin-1 assemblies regulate the fate of skeletal stem cells (aka, mesenchymal stem cells [MSCs]) by modulating TGFβ activity within the microenvironment of adult bone marrow niches. Since MSCs can also influence hematopoietic stem cell (HSC) activities, here we investigated adult hematopoiesis in mice with Cre-mediated inactivation of the fibrillin-1 (Fbn1) gene in the mesenchyme of the forming limbs (Fbn1(Prx1-/-) mice). Analyses of 3-month-old Fbn1(Prx1-/-) mice revealed a statistically significant increase of circulating red blood cells, which a differentiation assay correlated with augmented erythropoiesis. This finding, together with evidence of fibrillin-1 deposition in erythroblastic niches, supported the notion that this extracellular matrix protein normally restricts differentiation of erythroid progenitors. Whereas flow cytometry measurements identified a decreased HSC frequency in mutant relative to wild type mice, no appreciable differences were noted with regard to the relative abundance and differentiation potential of myeloid progenitor cells. Together these findings implied that fibrillin-1 normally promotes HSC expansion but does not influence cell lineage commitment. Since local TGFβ hyperactivity has been associated with abnormal osteogenesis in Fbn1(Prx1-/-) mice, 1-month-old mutant and wild type animals were systemically treated for 8weeks with either a pan-TGF-β-neutralizing antibody or an antibody of the same IgG1 isotype. The distinct outcomes of these pharmacological interventions strongly suggest that fibrillin-1 differentially modulates TGFβ activity in HSC vs. erythroid niches.

  3. Aerobic nitroreduction of dehydrochloramphenicol by bone marrow.

    Science.gov (United States)

    Isildar, M; Abou-Khalil, W H; Jimenez, J J; Abou-Khalil, S; Yunis, A A

    1988-06-30

    It has been previously demonstrated that dehydrochloramphenicol (DH-CAP), a bacterial metabolite of chloramphenicol, induces DNA single strand breaks in intact cells and is profoundly more cytotoxic than chloramphenicol (CAP). In view of previous observations relating genotoxicity of nitrocompounds to their nitroreduction by the target tissue, we studied the nitroreduction of DH-CAP by human and rabbit bone marrow. Nitroreduction by tissue homogenates was determined by the Bratton Marshall colorimetric assay and by high-performance liquid chromatography (HPLC). Nitroreduction of DH-CAP by bone marrow cell homogenates was observed under aerobic conditions and the reduction was both cell concentration- and time-dependent. The formation of the amino product aminodehydrochloramphenicol was confirmed by HPLC. Reduction by other tissues including human liver, Raji cells, and HL-60 tumors was also observed. These results suggest that genotoxicity of DH-CAP may be related to its nitroreduction by the target tissue with in situ production of toxic intermediates. Together with previous studies, these observations lend support to the thesis that the p-NO2 group may be the structural feature underlying aplastic anemia from CAP.

  4. 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 f

  5. Neuroamines — regulators of local processes at bone marrow autotransplantation

    Directory of Open Access Journals (Sweden)

    Vorobyova O.V.

    2015-12-01

    Full Text Available Purpose: to determine the content of neuroamines (histamine, serotonin, catecholamines in bioamine structures of bone marrow after autotransplantation. Material and methods. Animals were injected into the tail vein of bone marrow suspension obtained from the femur of the same mouse. It was taken from the femoral bone marrow of 1 ml and placed in 2 ml of physiological saline and thoroughly stirred. 1 ml of bone marrow suspension was injected into the tail vein. Cryostat sections were treated with luminescent-histochemical methods. Results. After bone marrow autotransplantation marked changes were observed in the neurotransmitters of the bone marrow — an increasing number of granular luminescent cells decrease in the amount of granules in them, and a decrease in the number of mast cells because of their degranulation. A weak luminescence was determined in nuclei in neutrophils. Perhaps this proves the activation of the immune response. Conclusion. The bone marrow autotransplantation leads to a redistribution of the structures of the bone marrow of histamine, catecholamines and serotonin, which changes the direction of cytodifferentiation, the content of neuroamines in granular luminescent cells and mast cells (cells of autonomic regulation.

  6. Prospective study of bone marrow in haematological disorders

    Directory of Open Access Journals (Sweden)

    Bhagya Lakshmi Atla

    2015-08-01

    Conclusion: The present study showed the usefulness of bone marrow aspiration and trephine biopsy in evaluation of the bone marrow in routine haematological disorders and also for understanding disease progression, for diagnosis and therapeutic evaluation. These are also helpful in planning further investigation and management. [Int J Res Med Sci 2015; 3(8.000: 1917-1921

  7. [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.

  8. 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.

  9. Glutamine supplementation in bone marrow transplantation.

    Science.gov (United States)

    Ziegler, Thomas R

    2002-01-01

    An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens.

  10. 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)

  11. 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.

  12. No narcosis for bone marrow harvest in autologous bone marrow transplantation.

    Science.gov (United States)

    de Vries, E G; Vriesendorp, R; Meinesz, A F; Mulder, N H; Postmus, P E; Sleijfer, D T

    1984-11-01

    A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation. This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.

  13. The adipocyte component of bone marrow in heterotopic bone induced by demineralized incisor grafts The adipocyte component of bone marrow in heterotopic bone induced by demineralized incisor grafts

    Directory of Open Access Journals (Sweden)

    Krzysztof H. Włodarski

    2012-10-01

    Full Text Available The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs. adipocytes was ascertained. The percentage of adipocytes in marrow
    increases over time. Such an effect, the replacement of myelopoietic marrow by adipogenic (yellow marrow
    and the resorption of induced bone, is observed in human osteoporosis. A decline in the non-adipogenic cell
    compartments of bone marrow accompanying induced bone begins in the fourth week of induction, gradually
    progresses until the 26th week, and does not change after that. The luminosity, a parameter used in image analysis
    and proportional to the number of nuclear cells, was 124 ± 3 in hematopoietic femoral bone marrow, and
    that of bone marrow of the induced bone was of a similar value (117 ± 8 in the fourth week. An evident decline
    in luminosity of bone marrow filling the foci of heterotopic bone was observed in samples taken at nine weeks
    (82 ± 20. This process progressed until the 26th week, reaching a luminosity of 70 ± 21. At the 42nd week, the
    luminosity remained at the same level (71 ± 27. This indicates that the replacement of hematopoietic bone
    marrow of heterotopically induced bone by unilocular adipocytes begins relatively early (the fourth week and is
    persistent.The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs

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

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L.; Horev, G.; Grunebaum, M. [Department of Imaging, Schneider Children`s Medical Center of Israel, Beilinson Medical Campus, 49202 Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel); Yaniv, I.; Stein, J.; Zaizov, R. [Department of Pediatric Hematology-Oncology, Schneider Children`s Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel)

    1997-11-01

    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.) With 1 fig., 2 tabs., 15 refs.

  15. Benzene-induced hematotoxicity and bone marrow compensation in B6C3F1 mice.

    Science.gov (United States)

    Farris, G M; Robinson, S N; Gaido, K W; Wong, B A; Wong, V A; Hahn, W P; Shah, R S

    1997-04-01

    Long-term inhalation exposure of benzene has been shown to cause hematotoxicity and an increased incidence of acute myelogenous leukemia in humans. The progression of benzene-induced hematotoxicity and the features of the toxicity that may play a major role in the leukemogenesis are not known. We report the hematological consequences of benzene inhalation in B6C3F1 mice exposed to 1, 5, 10, 100, and 200 ppm benzene for 6 hr/day, 5 days/week for 1, 2, 4, or 8 weeks and a recovery group. There were no significant effects on hematopoietic parameters from exposure to 10 ppm benzene or less. Exposure of mice to 100 and 200 ppm benzene reduced the number of total bone marrow cells, progenitor cells, differentiating hematopoietic cells, and most blood parameters. Replication of primitive progenitor cells in the bone marrow was increased during the exposure period as a compensation for the cytotoxicity induced by 100 and 200 ppm benzene. In mice exposed to 200 ppm benzene, the primitive progenitor cells maintained an increased percentage of cells in S-phase through 25 days of recovery compared with controls. The increased replication of primitive progenitor cells in concert with the reported genotoxicity induced by benzene provides the components necessary for producing an increased incidence of lymphoma in mice. Furthermore, we propose this mode of action as a biologically plausible mechanism for benzene-induced leukemia in humans exposed to high concentrations of benzene.

  16. Ex vivo expansions and transplantations of mouse bone marrow-derived hematopoietic stem/progenitor cells

    Institute of Scientific and Technical Information of China (English)

    王金福; 吴亦凡; HARRINTONGJenny; McNIECEIanK.

    2004-01-01

    To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic tem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded ells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF 1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells, CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded ceils by the co-culture with MSCs may result in more rapid engraftment ofneutrophils following infusion to transplant recipients.

  17. 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

  18. Marrow-tumor interactions: the role of the bone marrow in controlling chemically induced tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rosse, C

    1980-01-01

    This report summarizes work done to evaluate the role of the bone marrow in tumor growth regulation. Work done with the MCA tumor showed that several subclasses of mononuclear bone marrow cells (e.g. natural regulatory cell, NRC) play a major role in the regulation of tumor growth. Experiments with the spontaneous CE mammary carcinoma system illustrate that a rapid growth of certain neoplasms may be due to the fact that through some as yet undefined mechanism the tumor eliminates mononuclear cells in the bone marrow of the host and stops their production. (KRM)

  19. Lung-derived exosome uptake into and epigenetic modulation of marrow progenitor/stem and differentiated cells

    Directory of Open Access Journals (Sweden)

    Jason M. Aliotta

    2015-09-01

    Full Text Available Background: Our group has previously demonstrated that murine whole bone marrow cells (WBM that internalize lung-derived extracellular vesicles (LDEVs in culture express pulmonary epithelial cell–specific genes for up to 12 weeks. In addition, the lungs of lethally irradiated mice transplanted with lung vesicle–modulated marrow have 5 times more WBM-derived type II pneumocytes compared to mice transplanted with unmanipulated WBM. These findings indicate that extracellular vesicle modification may be an important consideration in the development of marrow cell–based cellular therapies. Current studies were performed to determine the specific marrow cell types that LDEV stably modify. Methods: Murine WBM-derived stem/progenitor cells (Lin-/Sca-1+ and differentiated erythroid cells (Ter119+, granulocytes (Gr-1+ and B cells (CD19+ were cultured with carboxyfluorescein N-succinimidyl ester (CFSE-labelled LDEV. LDEV+ cells (CFSE+ and LDEV− cells (CFSE− were separated by flow cytometry and visualized by fluorescence microscopy, analyzed by RT-PCR or placed into long-term secondary culture. In addition, murine Lin-/Sca-1+ cells were cultured with CFSE-labelled LDEV isolated from rats, and RT-PCR analysis was performed on LDEV+ and – cells using species-specific primers for surfactant (rat/mouse hybrid co-cultures. Results: Stem/progenitor cells and all of the differentiated cell types studied internalized LDEV in culture, but heterogeneously. Expression of a panel of pulmonary epithelial cell genes was higher in LDEV+cells compared to LDEV − cells and elevated expression of these genes persisted in long-term culture. Rat/mouse hybrid co-cultures revealed only mouse-specific surfactant B and C expression in LDEV+ Lin-/Sca-1+cells after 4 weeks of culture, indicating stable de novo gene expression. Conclusions: LDEV can be internalized by differentiated and more primitive cells residing in the bone marrow in culture and can induce stable de

  20. Bone marrow mesenchymal stromal cells induce nitric oxide synthase-dependent differentiation of CD11b+ cells that expedite hematopoietic recovery.

    Science.gov (United States)

    Trento, Cristina; Marigo, Ilaria; Pievani, Alice; Galleu, Antonio; Dolcetti, Luigi; Wang, Chun-Yin; Serafini, Marta; Bronte, Vincenzo; Dazzi, Francesco

    2017-02-09

    Bone marrow microenvironment is fundamental for hematopoietic homeostasis. Numerous efforts have been made to reproduce or manipulate its activity to facilitate engraftment after hematopoietic stem cell transplantation but clinical results remain unconvincing. This probably reflects the complexity of the hematopoietic niche. Recent data have demonstrated the fundamental role of stromal and myeloid cells in regulating hematopoietic stem cell self-renewal and mobilization in the bone marrow. In this study we unveil a novel interaction by which bone marrow mesenchymal stromal cells induce the rapid differentiation of CD11b+ myeloid cells from bone marrow progenitors. Such an activity requires the expression of nitric oxide synthase-2. Importantly, the administration of these mesenchymal stromal cells-educated CD11b+ cells accelerates hematopoietic reconstitution in bone marrow transplant recipients. We conclude that the liaison between mesenchymal stromal cells and myeloid cells is fundamental in hematopoietic homeostasis and suggests that it can be harnessed in clinical transplantation.

  1. Bone marrow invasion in multiple myeloma and metastatic disease.

    Science.gov (United States)

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  2. Bone marrow hypoplasia in a cat treated with griseofulvin.

    Science.gov (United States)

    Rottman, J B; English, R V; Breitschwerdt, E B; Duncan, D E

    1991-02-01

    Three weeks after initiation of griseofulvin treatment for dermatophytosis (40 mg/kg of body weight, q 12 h), an 8-yr-old domestic shorthair cat developed depression, vomiting, and pyrexia. Abnormalities found during physical examination included bilateral mydriasis, visual impairment, grade-II/V systolic murmur and multiple areas of alopecia. The cat was pancytopenic; serum biochemical abnormalities included hyperbilirubinemia, hyperglycemia, hyponatremia, and hypokalemia, and urinalysis revealed proteinuria, glycosuria, and bilirubinuria. Examination of a bone marrow aspirate revealed profound hypoplasia of all precursors. Griseofulvin toxicosis was diagnosed on the basis of the temporal relationship of drug administration with onset of clinical, hematologic, and biochemical abnormalities and failure to identify an infective or neoplastic cause for the bone marrow hypoplasia. The condition was refractory to treatment and the cat was euthanatized. Pathologic changes in the bone marrow were consistent with severe hypoplasia of all bone marrow precursors.

  3. Analysis of fatty acid composition in human bone marrow aspirates.

    Science.gov (United States)

    Deshimaru, Ryota; Ishitani, Ken; Makita, Kazuya; Horiguchi, Fumi; Nozawa, Shiro

    2005-09-01

    In the present study, the fatty acid composition of bone marrow aspirates and serum phospholipids in nine patients with hematologic diseases was investigated, and the effect of fatty acids on osteoblast differentiation in ST2 cells was examined. The concentrations of oleic acid and palmitic acid were significantly higher in bone marrow aspirates than in serum phospholipids, but the concentrations of other fatty acids did not differ. The rate of alkaline phosphatase positive ST2 cells induced by BMP2 was significantly increased by oleic acid, but was unaffected by the presence or absence of palmitic acid. We conclude that the fatty acid composition of bone marrow aspirates differs from that of serum phospholipids. This difference may affect osteoblast differentiation in the bone marrow microenvironment.

  4. Nonhematopoietic cells are the primary source of bone marrow-derived lung epithelial cells.

    Science.gov (United States)

    Kassmer, Susannah H; Bruscia, Emanuela M; Zhang, Ping-Xia; Krause, Diane S

    2012-03-01

    Previous studies have demonstrated that bone marrow (BM)-derived cells differentiate into nonhematopoietic cells of multiple tissues. To date, it remains unknown which population(s) of BM cells are primarily responsible for this engraftment. To test the hypothesis that nonhematopoietic stem cells in the BM are the primary source of marrow-derived lung epithelial cells, either wild-type hematopoietic or nonhematopoietic BM cells were transplanted into irradiated surfactant-protein-C (SPC)-null mice. Donor-derived, SPC-positive type 2 pneumocytes were predominantly detected in the lungs of mice receiving purified nonhematopoietic cells and were absent from mice receiving purified hematopoietic stem and progenitor cells. We conclude that cells contained in the nonhematopoietic fraction of the BM are the primary source of marrow-derived lung epithelial cells. These nonhematopoietic cells may represent a primitive stem cell population residing in adult BM.

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

    Directory of Open Access Journals (Sweden)

    David F Razidlo

    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.

  6. Advances in bone marrow stem cell therapy for retinal dysfunction.

    OpenAIRE

    Park, SS; Moisseiev, E; Bauer, G.; Anderson, JD; Grant, MB; Zam, A; Zawadzki, RJ; Werner., JS; Nolta, JA

    2017-01-01

    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 ret...

  7. Immune Cell Isolation from Mouse Femur Bone Marrow

    OpenAIRE

    Liu, Xiaoyu; Quan, Ning

    2015-01-01

    The bone marrow is the site of hematopoesis and contains mixed population of blood cells including erythrocytes, granulocytes, monocytes, dendritic cells, lymphocytes and hematopoietic stem cells. The following protocol provides a simple and fast method for isolation of bone marrow immune cells (no erythrocytes) from mouse femurs with a yield of approximate 8 × 107 cells in 5 ml culture media (1.6 × 104 cells/μl). Further isolation or flow cytometric analysis might be required for study of sp...

  8. Osteoclast activity modulates B-cell development in the bone marrow

    Institute of Scientific and Technical Information of China (English)

    Anna Mansour; Adrienne Anginot; Stéphane J C Mancini; Claudine Schiff; Georges F Carle; Abdelilah Wakkach; Claudine Blin-Wakkach

    2011-01-01

    B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.

  9. Osteoclast activity modulates B-cell development in the bone marrow.

    Science.gov (United States)

    Mansour, Anna; Anginot, Adrienne; Mancini, Stéphane J C; Schiff, Claudine; Carle, Georges F; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2011-07-01

    B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.

  10. Etiological Profile of Plasmacytosis on Bone Marrow Aspirates

    Directory of Open Access Journals (Sweden)

    Monika Gupta

    2016-03-01

    Full Text Available Objective: In recent years, during routine examination of bone marrow aspirates, an increased plasma cell per­centage has been noted in a good number of cases which included both neoplastic and non-neoplastic diseases. An attempt has been made to observe the spectra of condi­tions with plasmacytosis in bone marrow. Methods: The present study was conducted in the de­partment of pathology over a period of one year. A total of 114 bone marrow aspirates that showed increased plas­ma cells (>3.5% constitute the study material. A detailed relevant clinical examination followed by complete blood count, peripheral smear examination and bone marrow aspiration was done in all cases. Results: There was slight female predominance with male to female ratio of 1:1.1. The majority of patients were in 4th decade. The plasma cell concentration ranged from 5% to 36%. As far as the etiology is concerned, 96 cases (84.2% were non-neoplastic and 18 cases (15.7% had neoplastic etiology. Conclusion: Bone marrow plasmacytosis can present as diagnostic dilemma and some time can be challenging to differentiate reactive from neoplastic condition as there is an overlap both in counts and morphology. Each case with plasmacytosis especially in the overlap range requires complete clinical evaluation, individualized investigations and more specific tests like immunoelectrophoresis and bone marrow biopsy with immunohistochemistry to arrive at a final diagnosis for patient management.

  11. Pulmonary fungal infections after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Allan, B.T.; Patton, D.; Ramsey, N.K.C.; Day, D.L.

    1988-02-01

    Of 319 pediatric patients treated with bone marrow transplantation (BMT) during a 10-year period, 27 developed pulmonary fungal infections (PFI). Only 2 patients (7%) survived. Twenty-three patients (85%) had been treated with systemic anti-fungal therapy immediately before or at the time of diagnosis. Nineteen patients (70%) were neutropenic, and 4 of the 8 patients who were not neutropenic were being treated with systemic steroids for graft vs. host disease (GVHD). Seven patients (26%) died within 7 days of diagnosis. The diagnosis was made ante-mortem in 9 patients (33%). Radiographic abnormalities were variable. At the onset of chest X-ray (CXR) change, the pulmonary infiltrates were unilateral in 14 patients (52%) and, at diagnosis, bilateral in 18 (66%). At diagnosis the infiltrates were interstitial in 3 patients (11%), alveolar in 20 (74%) and mixed in 4 (15%). Six patients (22%) developed cavitary lesions. The infecting agents were Aspergillus in 21 patients (78%), Candida in 7 (26%), Mucormycosis in 3 (11%), and Fusarium in 1 (4%). Five patients (19%) had mixed fungal infections and 7 (26%) had concurrent cytomegalovirus (CMV) pulmonary infections. Although the radiographic changes are often nonspecific in PFI, alveolar or nodular infiltrates in neutropenic patients or in those being treated for GVHD should strongly suggest a fungal etiology.

  12. 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. PMID:28286502

  13. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  14. Diffuse Hypermetabolism at Bone Marrow in F-18 FDG PET/CT: Correlation with Bone Marrow Biopsy and Complete Blood Cell Counts

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yun Hee; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2009-02-15

    Increased FDG uptake in the bone marrow has been reported in patients taking erythropoietin or granulocyte-colony stimulating factor (G-CSF). The aim of this study is to investigate the correlation between F-18 FDG uptake in the bone marrow and bone marrow finding, hematological parameters. Twenty patients who had diffuse FDG uptake at the bone marrow and received hematological examinations, bone marrow biopsy within 10 days before or after PET/CT were enrolled in this study. Among them, 11 patients were excluded; 4 patients received G-CSF or erythropoietin before PET/CT. Seven patients showed definite pathology in a bone marrow biopsy. The parameters included the measurement of WBC, hemoglobin, platelet and cellularity of the bone marrow. Bone marrow FDG uptake was correlated with a low hemoglobin but not WBC, platelet. Histopathologic findings in marrow biopsies were various: normal finding (n=3), hyperplasia of granulocytic cells (n=2), eosinophilic hyperplasia (n=1), reactive lymphoid nodules (n=1), hypercelluar marrow (n=1), hypocelluar marrow (n=1). All patients except two, showed normal marrow celluarity. FDG uptake by bone marrow correlated with anemia but not WBC, platelet, bone marrow cellularity.

  15. 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.

  16. Bone Marrow Homing Enriches Stem Cells Responsible for Neogenesis of Insulin-Producing Cells, While Radiation Decreases Homing Efficiency.

    Science.gov (United States)

    Goldenberg-Cohen, Nitza; Iskovich, Svetlana; Askenasy, Nadir

    2015-10-01

    Small-sized adult bone marrow cells isolated by counterflow centrifugal elutriation and depleted of lineage markers (Fr25lin(-)) have the capacity to differentiate into insulin-producing cells and stabilize glycemic control. This study assessed competitive migration of syngeneic stem cells to the bone marrow and islets in a murine model of chemical diabetes. VLA-4 is expressed in ∼ 25% of these cells, whereas CXCR4 is not detected, however, it is transcriptionally upregulated (6-fold). The possibility to enrich stem cells by a bone marrow homing (BM-H) functional assay was assessed in sequential transplants. Fr25lin(-) cells labeled with PKH26 were grafted into primary myeloablated recipients, and mitotically quiescent Fr25lin(-)PKH(bright) cells were sorted from the bone marrow after 2 days. The contribution of bone marrow-homed stem cells was remarkably higher in secondary recipients compared to freshly elutriated cells. The therapeutic efficacy was further increased by omission of irradiation in the secondary recipients, showing a 25-fold enrichment of islet-reconstituting cells by the bone marrow homing assay. Donor cells identified by the green fluorescent protein (GFP) and a genomic marker in sex-mismatched transplants upregulated PDX-1 and produced proinsulin, affirming the capacity of BM-H cells to convert in the injured islets. There was no evidence of transcriptional priming of freshly elutriated subsets to express PDX-1, insulin, and other markers of endocrine progenitors, indicating that the bone marrow harbors stem cells with versatile differentiation capacity. Affinity to the bone marrow can be used to enrich stem cells for pancreatic regeneration, and reciprocally, conditioning reduces the competitive incorporation in the injured islets.

  17. Effects of Platelet Factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    孟凡凯; 孙汉英; 刘文励; 袁慧玲; 徐惠珍; 孙岚; 周银莉; 任天华

    2002-01-01

    Summary: To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic BMT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU-S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4-treated groups, the CFU-S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT (P<0. 01 or P<0. 05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.

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

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yoh; Magara, Tatsuo; Kobayashi, Hiroaki; Ichihashi, Takumi; Hikishima, Hiroshi (Kanazawa Univ. (Japan). School of Medicine)

    1984-03-01

    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.

  19. 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...... patients with myelofibrosis differed from that in samples from controls. DESIGN AND METHODS: We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models...... of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin). RESULTS: In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (pvessels displayed 5.9-fold larger mean...

  20. 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.

  1. 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.

  2. Correlation of plasma FL expression with bone marrow irradiation dose.

    Directory of Open Access Journals (Sweden)

    Mary Sproull

    Full Text Available PURPOSE: Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure. MATERIALS/METHODS: C57BL6 mice received a single whole body or partial body irradiation dose of 1-8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1-3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose. RESULTS: At all doses between 1-8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation. CONCLUSION: Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.

  3. 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 RATIONALE: 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. OBJECTIVE: We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity. METHODS AND RESULTS: 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. CONCLUSIONS: Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  4. Robust growth of avirulent phase II Coxiella burnetii in bone marrow-derived murine macrophages

    Science.gov (United States)

    Cockrell, Diane C.; Long, Carrie M.; Robertson, Shelly J.; Shannon, Jeffrey G.; Miller, Heather E.; Myers, Lara; Larson, Charles L.; Starr, Tregei; Beare, Paul A.

    2017-01-01

    Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent phase I, Coxiella burnetii. Growth restriction of phase II bacteria is thought to result from potentiated recognition of pathogen-associated molecular patterns, which leads to production of inhibitory effector molecules. Past studies have used conditioned medium from L-929 murine fibroblasts as a source of macrophage-colony stimulating factor (M-CSF) to promote differentiation of bone marrow-derived myeloid precursors into macrophages. However, uncharacterized components of conditioned medium, such as variable amounts of type I interferons, can affect macrophage activation status and their permissiveness for infection. In the current study, we show that the C. burnetii Nine Mile phase II (NMII) strain grows robustly in primary macrophages from C57BL/6J mice when bone marrow cells are differentiated with recombinant murine M-CSF (rmM-CSF). Bacteria were readily internalized by BMDM, and replicated within degradative, LAMP1-positive vacuoles to achieve roughly 3 logs of growth over 6 days. Uninfected BMDM did not appreciably express CD38 or Egr2, markers of classically (M1) and alternatively (M2) activated macrophages, respectively, nor did infection change the lack of polarization. In accordance with an M0 phenotype, infected BMDM produced moderate amounts of TNF and nitric oxide. Similar NMII growth results were obtained using C57BL/6J myeloid progenitors immortalized with an estrogen-regulated Hoxb8 (ER-Hoxb8) oncogene. To demonstrate the utility of the ER-Hoxb8 system, myeloid progenitors from natural resistance-associated macrophage protein 1 (Nramp1) C57BL/6J knock-in mice were transduced with ER-Hoxb8, and macrophages were derived from immortalized progenitors using rmM-CSF and infected with NMII. No difference in growth was observed when compared to macrophages from wild type mice, indicating depletion of metal ions by the Nramp1

  5. IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow stromal cells.

    Science.gov (United States)

    Kim, Beom-Su; Kim, Hyung-Jin; Kim, Jin Seong; You, Yong-Ouk; Zadeh, Homa; Shin, Hong-In; Lee, Seung-Jin; Park, Yoon-Jeong; Takata, Takashi; Pi, Sung-Hee; Lee, Jun; You, Hyung-Keun

    2012-09-01

    The exact molecular mechanisms governing the differentiation of bone marrow stromal stem/progenitor cells (BMSCs) into osteoblasts remain largely unknown. In this study, a highly expressed protein that had a high degree of homology with interferon-induced transmembrane protein 1 (IFITM1) was identified using differentially expressed gene (DEG) screening. We sought to determine whether IFITM1 influenced osteoblast differentiation. During differentiation, IFITM1 expression gradually increased from 5 to 10days and subsequently decreased at 15 days in culture. Analysis of IFITM1 protein expression in several cell lines as well as in situ studies on human tissues revealed its selective expression in bone cells and human bone. Proliferation of human alveolar-derived bone marrow stromal cells (hAD-BMSCs) was significantly inhibited by IFITM1 knockdown by using short hairpin RNA, as were bone specific markers such as alkaline phosphatase, collagen type I α 1, bone sialoprotein, osteocalcin, and osterix were decreased. Calcium accumulation also decreased following IFITM1 knockdown. Moreover, IFITM1 knockdown in hAD-BMSCs was associated with inhibition of Runx2 mRNA and protein expression. Collectively, the present data provide evidence for the role of IFITM1 in osteoblast differentiation. The exact mechanisms of IFITM1's involvement in osteoblast differentiation are still under investigation.

  6. Concentration of bone marrow mononuclear cells for in vitro treatment and AB0-incompatible transplantation: a rapid and reproducible procedure using the haemonetics V50 cell separator.

    Science.gov (United States)

    Wiesneth, M; Hertenstein, B; Koerner, K; Heimpel, H; Heit, W

    1988-01-01

    Forty-nine allogeneic and 14 autologous bone marrow grafts were processed with the Haemonetics V50 cell separator (Haemonetics Corp., Braintree, USA) for in vitro treatment with antibodies and cryopreservation respectively. The concentration of hemopoietic progenitor cells was performed without any sedimentation or density gradient agents. The recovery is given in percent (mean +/- sd) of the original marrow values: mononuclear cells (MNC) 74 +/- 10%, polymorphonuclear cells (PMC) 48 +/- 17%, red blood cells (RBC) 12 +/- 5%, granulocyte/monocyte progenitors (CFU-GM) 83 +/- 36%, and erythroid progenitors (BFU-E) 78 +/- 38%. The recovery of nucleated cells (NC) was 90 +/- 13% and the viability 82 +/- 11% after cryopreservation. The technique described provides a simple, rapid and efficient preparation of large bone marrow volumes for in vitro treatment and AB0-incompatible transplantation.

  7. Bone marrow granulomas in infiltrating lobular breast cancer.

    OpenAIRE

    Kettle, P.; Allen, D C

    1997-01-01

    A 50 year old woman with a history of infiltrating lobular breast carcinoma presented with back pain. Bone scan and magnetic resonance imaging were not conclusive. A bone marrow aspirate appeared normal. A routine trephine biopsy specimen showed granulomas but no obvious infiltration by carcinoma. Immunohistochemical staining with epithelial markers demonstrated carcinoma cells in the trephine specimen. This case illustrates the difficulty of detecting infiltrating lobular carcinoma in bone m...

  8. A Survey of Bacterial Infections in Bone Marrow Transplant Recipients

    Directory of Open Access Journals (Sweden)

    MH Shirazi

    2007-09-01

    Full Text Available "nBackground: Bone marrow transplant (BMT recipients are prone to bacterial, viral and fungal infections. Bacterial infec­tion is considered as one of the common and serious complications in bone marrow transplant recipients. The aim of this study was to determine the rate of bacterial infections in bone marrow transplant recipients."nMethods: Fifty-two blood and 25 catheter samples were obtained from 23 patients who were hospitalized in bone marrow trans­plantation unit in Shariati Hospital in Tehran. Bacterial strains were isolated and identified by the standard conven­tional bacteriological methods. Antimicrobial susceptibility was performed according to the guidelines from NCCLS using 18 different antibiotics."nResults:  The strains of Staphylococci, Streptococcus viridans, Pseudomonas aeruginosa and Escherichia coli were isolated from 8(66.7%, 1(8.3%, 2 (16.7% and the 1(8.3% cases, respectively."nConclusion: Current study indicated that the bacterial infections particularly those caused by the Gram-positive cocci were still as important problem in bone marrow transplant.

  9. La diabetes altera el potencial osteogénico de células progenitoras de médula ósea: Efectos del tratamiento con metformina Diabetes Decreases the Osteogenic Potential of Bone Marrow Progenitor Cells: Effects of Treatment with Metformin

    Directory of Open Access Journals (Sweden)

    MJ Tolosa

    2012-06-01

    incidence of non-traumatic fractures has been particularly observed in patients with type 2 diabetes. Recently, we have demonstrated that metformin has in vitro and in vivo osteogenic effects: (a it stimulates the proliferation, differentiation and mineralization of osteoblasts in culture, and (b in non-diabetic rats, it increases the repair of minimal bone lesions and improves femoral trabecular bone microarchitecture. In this study, we evaluated in rats the effect of diabetes induction by a partial destruction of pancreatic beta cells, on the osteogenic commitment of bone marrow progenitor cells (BMPC, and the modulation of this effect by orally administered metformin. We used young male Sprague Dawley rats (200 g, divided into four groups: untreated non-diabetic controls [C], non-diabetic rats treated for 2 weeks with metformin administered in drinking water (100 mg/kg/day [M], untreated diabetic rats [D], and diabetic rats treated for 2 weeks with metformin (100 mg/kg/day [DM]. Induction of Diabetes was performed one week prior to treatment with metformin, by successive intraperitoneal injections with 75 mg/kg body weight of nicotinic acid and 60 mg/kg body weight of streptozotocin. At the end of all treatments, blood samples were obtained to confirm the development of Diabetes, after which the animals were sacrificed by cervical dislocation under anesthesia. Femora and/or tibiae were dissected, and bone marrow cells were collected by flushing the bone diaphysal canal with Dulbecco's modified essential medium (DMEM under sterile conditions. Adherent cells were grown to confluence in DMEM-10 % fetal bovine serum (FBS, after which we assessed alkaline phosphatase specific activity (ALP by an enzymatic kinetic method, and type 1 collagen production (Col-1 by a Sirius Red colorimetric method (basal osteoblastic differentiation of BMPC. Subsequently, BMPC were submitted to an osteogenic induction for 15 days with an osteogenic medium (DMEM-10 % FBS containing ascorbic acid

  10. In vivo visualizing the dynamics of bone marrow stem cells in mouse retina and choroidal-retinal circulation

    Science.gov (United States)

    Wang, Heuy-Ching H.; Zwick, Harry; Edsall, Peter R.; Cheramie, Rachel D.; Lund, David J.; Stuck, Bruce

    2007-02-01

    It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. Therefore it is an attractive therapeutic intervention to apply autologous bone marrow-derived stem cells that may offer neuroprotection to laser-induced retinal injuries. The purpose of this study is to develop a method with which to visualize bone marrow stem cells dynamics in mouse retinal circulation. We have used a physiological method, confocal scanning laser ophthalmoscope (SLO), to track the highly enriched stem/progenitor cells circulating in the retina. Stem cells were enriched by immunomagnetic depletion of cells committed to the T- and B lymphocytic, myeloid and erythorid lineages. CellTracker TM Green-labeled stem cells were injected into the tail veins of mice with laser-induced focal retinal injuries. Bone marrow stem cells labeled with CellTracker TM Green were visible in the retinal circulation for as long as 1 hour and 30 minutes. These studies suggest that stem cell-enriched bone marrow cells may have the ability to mobilize into laser-induced retinal injuries and possibly further proliferate, differentiate and functionally integrate into the retina.

  11. Loss of c-Kit and bone marrow failure upon conditional removal of the GATA-2 C-terminal zinc finger domain in adult mice.

    Science.gov (United States)

    Li, Haiyan S; Jin, Jin; Liang, Xiaoxuan; Matatall, Katie A; Ma, Ying; Zhang, Huiyuan; Ullrich, Stephen E; King, Katherine Y; Sun, Shao-Cong; Watowich, Stephanie S

    2016-09-01

    Heterozygous mutations in the transcriptional regulator GATA-2 associate with multilineage immunodeficiency, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The majority of these mutations localize in the zinc finger (ZnF) domains, which mediate GATA-2 DNA binding. Deregulated hematopoiesis with GATA-2 mutation frequently develops in adulthood, yet GATA-2 function in the bone marrow remains unresolved. To investigate this, we conditionally deleted the GATA-2 C-terminal ZnF (C-ZnF) coding sequences in adult mice. Upon Gata2 C-ZnF deletion, we observed rapid peripheral cytopenia, bone marrow failure, and decreased c-Kit expression on hematopoietic progenitors. Transplant studies indicated GATA-2 has a cell-autonomous role in bone marrow hematopoiesis. Moreover, myeloid lineage populations were particularly sensitive to Gata2 hemizygosity, while molecular assays indicated GATA-2 regulates c-Kit expression in multilineage progenitor cells. Enforced c-Kit expression in Gata2 C-ZnF-deficient hematopoietic progenitors enhanced myeloid colony activity, suggesting GATA-2 sustains myelopoiesis via a cell intrinsic role involving maintenance of c-Kit expression. Our results provide insight into mechanisms regulating hematopoiesis in bone marrow and may contribute to a better understanding of immunodeficiency and bone marrow failure associated with GATA-2 mutation.

  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. Scanning electron microscopy of erythropoietin-stimulated bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Leblond, P.F. (Hospital of St. Sacrement, Quebec); Chamberlain, J.K.; Weed, R.I.

    1975-01-01

    This work describes and illustrates the scanning electron microscopic modifications observed in the femoral bone marrow of normal mice 72 hours after a single injection of partly purified sheep erythropoietin and of mice afflicted with a chronic congenital hemolytic anemia analogous to the disease Hereditary Spherocytosis in man. In acordance with previous transmission electron microscopic studies, the observations are consistent with an effect of erythropoietin both on the frequency of cell migration across the normally intact marrow sinus endothelium and on the morphology of sinus adventitial cells. It is suggested that these ultrastructural modifications may be responsible for the greater patency of the marrow-blood barrier under erythropoietin stimulation.

  14. Bone marrow edema syndrome in postpartal women: treatment with iloprost.

    Science.gov (United States)

    Aigner, Nicholas; Meizer, Roland; Meraner, Dominik; Becker, Stephan; Meizer, Elizabeth; Landsiedl, Franz

    2009-04-01

    Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing. Relief from pain, restoration of functional capacity, and normalization of the MRI signal pattern were rapidly achieved, thus avoiding the need for surgical intervention. As the substance is contraindicated in pregnancy, therapy may begin only some days after parturition, with a short discontinuation in breastfeeding.

  15. 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.

  16. 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

  17. 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

  18. Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Qiao, Jianlin; Wu, Jinyan; Li, Yuanyuan; Xia, Yuan; Chu, Peipei; Qi, Kunming; Yan, Zhiling; Yao, Haina; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2016-01-01

    Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1β, IL-18, TNF-α and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes.

  19. Tissue engineering bone using autologous progenitor cells in the peritoneum.

    Directory of Open Access Journals (Sweden)

    Jinhui Shen

    Full Text Available Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs in the peritoneal lavage fluid from mice with peritoneal catheter implants. The osteogenic potential of these peritoneal progenitor cells was demonstrated by their ability to easily infiltrate decalcified bone implants, produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when poly(l-lactic acid scaffolds loaded with bone morphogenetic protein-2 (a known osteogenic differentiation agent were implanted into the peritoneum, signs of osteogenesis were seen within 8 weeks of implantation. The results of this investigation support the concept that scaffolds containing BMP-2 can stimulate the formation of bone in the peritoneum via directed autologous stem and progenitor cell responses.

  20. Genetic response and morphologic characterization of chicken bone-marrow derived dendritic cells during infection with high and low pathogenic avian influenza viruses

    Science.gov (United States)

    Dendritic cells (DC) are professional antigen-presenting cells of the immune system that function to initiate primary immune responses. Progenitors of DCs are derived from haematopoietic stem cells in the bone marrow (BM) that migrate in non-lymphoid tissues to develop into immature DCs. Here, they ...

  1. 兔骨髓源单个核细胞诱导血管内皮祖细胞修复尿道缺损%Bone marrow mononuclear cells-differentiated vascular endothelial progenitor cells for urethral defect repair in rabbits

    Institute of Scientific and Technical Information of China (English)

    张谦; 单岩; 李泸平; 范应中; 王家祥

    2008-01-01

    BACKGROUND: How to solve the source of material substitute for repair of urethral dcfoct and improve the blood supply of new urethra has become a critical problem in the urethral repair and reconstruction.OBJECTIVE: To investigate the effects of endothelial progenitor cells (EPCs) on improving blood circulation in the new urethra following urethral defect repair.DESIGN,TIME AND SETTING: In vivo tissue engineering experiment,performed at the Laboratory of Deparanent of Surgery,First Affiliated Hospital of Zhengzhou University between January 2006 and February 2008.MATERIALS: Thirteen 3-5-month-old male Japanese rabbits were included for this study.Of them,one was used for preparation of bone marrow mononuclear cells,and the remaining twelve rabbits were divided into EPC repair group (n=8) and model group (n=4).METHODS: Under the aseptic condition,bone marrow was taken from the rabbit bilateral anterior superior lilac spine.Mononuclear cells isolated by Percoll method were induced in vitro using medium supplemented with vascular endothelial growth factors (VEGFs) and bovine basic fihroblast growth factors.When covering the whole bottom of culture flask,the mononuclear cells were digested with trypsin for passage.Animal models of urethral defect were developed in the two groups.One piece of aseptic fresh acellular human amnion (1 cm2) was sutured to each defected urethra using 0/6 DG suture for forming urethra.In the EPC repair group,1010/L passage 3 rabbit bone marrow mononuclear cell suspension was injected to two anastomotic stomas of the new urethra,0.1 mL for each stoma.The subcutaneous tissue was interruptedly sutured to the formed urethra using 0/6 DG suture.In addition,0.5 mL bone marrow mononuclear cell suspension was added to the region between each anastomotic stroma and newly repaired urethra.The same procedure was performed in the model group except that bone marrow mononuclear cell suspension was replaced by cell-free medium.At weeks 4 and 12 after

  2. A study of bone marrow failure syndrome in children

    Directory of Open Access Journals (Sweden)

    Gupta V

    2008-01-01

    Full Text Available Background: Bone marrow failure syndrome (BMFS, or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. Aim: To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. Setting and Design: This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. Materials and Methods: Children with pancytopenia (Hb < 10 g/dl, absolute neutrophil count < 1.5 x 10 9 /L, platelet count < 100 x 10 9 /L and bone marrow cellularity < 25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. Statistical Analysis: Relative risk was estimated by odds ratio (OR with 95% confidence interval (CI in matched cases and controls. Results: Of the 53 children studied, 6 (11.3% were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8% had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father′s occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. Conclusion: Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.

  3. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?★

    OpenAIRE

    Li, Yi; Hua, Xuming; Hua, Fang; Mao, Wenwei; Wan, Liang; Li, Shiting

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohist...

  4. Late effects on human bone marrow after extended field radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, C.; Morardet, N.; Tubiana, M.

    1983-09-01

    Thirty-two patients with lymphoma were treated by extended radiotherapy (RT) at a dose of 40 Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT. The hypoactivity persisted even when the hemopoietic tissues had been subjected to the intense stimulation provoked by an aplasia caused by chemotherapy. However, a recovery was observed for dose of 20 Gy or lower. The hemopoietic activity of the irradiated bone marrow appears to be related to the volume of the marrow irradiated and is higher after a mantle + inverted Y field than after a mantle field. Bone marrow scintigraphies with /sup 59/Fe in 7 out of 9 patients studied revealed an extension of hematopoiesis into a normally dormant area of the marrow, such as the femora. In 2 patients an erythropoietic activity was observed in spleens which had received a dose of 40 Gy, and extra medullary erythropoiesis was found in approximately two-thirds of the patients.

  5. Bone Marrow Transplantation for Severe Aplastic Anemia Secondary to Temozolomide

    OpenAIRE

    Morris, E. Brannon; Kasow, Kimberly; Reiss, Ulrike; Ellison, David; Broniscer, Alberto

    2008-01-01

    Radiotherapy (RT) and concomitant/adjuvant therapy with temozolomide (Temodar) is a common treatment regimen for children and adults with glioma. Although temozolomide is generally well tolerated with temporary myelosuppression as the primary dose-limiting toxicity, irreversible bone-marrow aplasia after treatment with temozolomide has been reported. We report the case of an adolescent patient with a high-grade glioma who, after > 2 years of event-free survival, underwent successful bone marr...

  6. File list: ALL.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Leukemic_bone_marrow mm9 All antigens Blood Leukemic bone marrow S...261 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  7. File list: His.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Leukemic_bone_marrow mm9 Histone Blood Leukemic bone marrow SRX471...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  8. File list: DNS.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.Leukemic_bone_marrow mm9 DNase-seq Blood Leukemic bone marrow http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  9. File list: ALL.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Leukemic_bone_marrow mm9 All antigens Blood Leukemic bone marrow S...251 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  10. File list: ALL.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Leukemic_bone_marrow mm9 All antigens Blood Leukemic bone marrow S...243 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  11. File list: Unc.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Leukemic_bone_marrow mm9 Unclassified Blood Leukemic bone marrow h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  12. File list: Unc.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Leukemic_bone_marrow mm9 Unclassified Blood Leukemic bone marrow h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  13. File list: DNS.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.Leukemic_bone_marrow mm9 DNase-seq Blood Leukemic bone marrow http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  14. File list: His.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Leukemic_bone_marrow mm9 Histone Blood Leukemic bone marrow SRX471...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  15. File list: Unc.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Leukemic_bone_marrow mm9 Unclassified Blood Leukemic bone marrow h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  16. File list: Unc.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Bone_Marrow_Cells hg19 Unclassified Blood Bone Marrow Cells SRX104...047338,SRX1047346,SRX1047345,SRX1047347,SRX1047348,SRX1047349,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  17. File list: Pol.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.Bone_Marrow_Cells mm9 RNA polymerase Blood Bone Marrow Cells SRX06...2947,SRX143852 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  18. File list: His.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Bone_Marrow_Cells mm9 Histone Blood Bone Marrow Cells SRX306591,SR...RX1156596,SRX1156598,SRX1156595,SRX692969,SRX1156602,SRX692971,SRX306594,SRX306593 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  19. File list: Oth.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Bone_Marrow_Cells mm9 TFs and others Blood Bone Marrow Cells SRX06...130271,SRX209469,SRX209468,SRX036744,SRX036745 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  20. File list: Unc.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Bone_Marrow_Cells mm9 Unclassified Blood Bone Marrow Cells SRX1302...72 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  1. File list: Unc.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Bone_Marrow_Cells hg19 Unclassified Blood Bone Marrow Cells SRX104...047349,SRX1047340,SRX1047339,SRX1047336,SRX1047338,SRX1047332,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  2. File list: Unc.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Bone_Marrow_Cells mm9 Unclassified Blood Bone Marrow Cells SRX1302...72 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  3. File list: ALL.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Bone_Marrow_Cells hg19 All antigens Blood Bone Marrow Cells SRX104...047349,SRX1047340,SRX1047339,SRX1047336,SRX1047338,SRX1047332,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  4. File list: ALL.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Bone_Marrow_Cells hg19 All antigens Blood Bone Marrow Cells SRX104...047338,SRX1047346,SRX1047345,SRX1047347,SRX1047348,SRX1047349,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  5. File list: Oth.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Bone_Marrow_Cells mm9 TFs and others Blood Bone Marrow Cells SRX48...036744,SRX487081,SRX036745,SRX487083,SRX209469 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  6. File list: Oth.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Bone_Marrow_Cells mm9 TFs and others Blood Bone Marrow Cells SRX48...130271,SRX209469,SRX209468,SRX036744,SRX036745 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  7. File list: Unc.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Bone_Marrow_Cells hg19 Unclassified Blood Bone Marrow Cells SRX104...047341,SRX1047332,SRX1047346,SRX1047345,SRX1047347,SRX1047349,SRX1047348 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  8. File list: Oth.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Bone_Marrow_Cells hg19 TFs and others Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  9. File list: ALL.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Bone_Marrow_Cells mm9 All antigens Blood Bone Marrow Cells SRX4870...36746 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  10. File list: ALL.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Bone_Marrow_Cells mm9 All antigens Blood Bone Marrow Cells SRX0629...09471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  11. File list: Pol.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.Bone_Marrow_Cells mm9 RNA polymerase Blood Bone Marrow Cells SRX14...3852,SRX062947 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  12. File list: ALL.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Bone_Marrow_Cells hg19 All antigens Blood Bone Marrow Cells SRX104...047340,SRX1047338,SRX1047336,SRX1047332,SRX1047339,SRX1047327,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  13. File list: ALL.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Bone_Marrow_Cells mm9 All antigens Blood Bone Marrow Cells SRX4870...09471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  14. File list: Oth.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Bone_Marrow_Cells hg19 TFs and others Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  15. File list: His.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Bone_Marrow_Cells mm9 Histone Blood Bone Marrow Cells SRX306591,SR...1156598,SRX1156601,SRX1156596,SRX1156602,SRX1156597,SRX1156595,SRX692969,SRX692971 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  16. File list: Pol.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Bone_Marrow_Cells mm9 RNA polymerase Blood Bone Marrow Cells SRX14...3852,SRX062947 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  17. File list: Unc.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Bone_Marrow_Cells mm9 Unclassified Blood Bone Marrow Cells SRX1302...72 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  18. File list: Pol.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Bone_Marrow_Cells hg19 RNA polymerase Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  19. File list: Oth.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Bone_Marrow_Cells mm9 TFs and others Blood Bone Marrow Cells SRX48...487083,SRX811397,SRX225200,SRX130271,SRX209468 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  20. File list: Unc.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Bone_Marrow_Cells mm9 Unclassified Blood Bone Marrow Cells SRX1302...72 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  1. File list: His.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Bone_Marrow_Cells mm9 Histone Blood Bone Marrow Cells SRX1156599,S...SRX692972,SRX1156597,SRX1156595,SRX306594,SRX692971,SRX1156602,SRX692969,SRX306593 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  2. File list: Pol.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Bone_Marrow_Cells mm9 RNA polymerase Blood Bone Marrow Cells SRX06...2947,SRX143852 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  3. File list: Pol.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Bone_Marrow_Cells hg19 RNA polymerase Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  4. File list: His.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Bone_Marrow_Cells mm9 Histone Blood Bone Marrow Cells SRX062946,SR...02,SRX692969,SRX306598,SRX306599,SRX306593,SRX692970,SRX692972,SRX306594,SRX692971 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  5. File list: ALL.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Bone_Marrow_Cells mm9 All antigens Blood Bone Marrow Cells SRX4870...36746 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  6. File list: Oth.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Bone_Marrow_Cells hg19 TFs and others Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  7. File list: Pol.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.Bone_Marrow_Cells hg19 RNA polymerase Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  8. File list: Oth.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Bone_Marrow_Cells hg19 TFs and others Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  9. File list: Unc.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Bone_Marrow_Cells hg19 Unclassified Blood Bone Marrow Cells SRX104...047340,SRX1047338,SRX1047336,SRX1047332,SRX1047339,SRX1047327,SRX1047341 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  10. File list: ALL.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Bone_Marrow_Cells hg19 All antigens Blood Bone Marrow Cells SRX104...047341,SRX1047332,SRX1047346,SRX1047345,SRX1047347,SRX1047349,SRX1047348 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  11. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

    Science.gov (United States)

    A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

  12. File list: Pol.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Leukemic_bone_marrow mm9 RNA polymerase Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  13. File list: His.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Leukemic_bone_marrow mm9 Histone Blood Leukemic bone marrow SRX471...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  14. File list: Oth.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Leukemic_bone_marrow mm9 TFs and others Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  15. File list: Oth.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Leukemic_bone_marrow mm9 TFs and others Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  16. File list: Pol.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.Leukemic_bone_marrow mm9 RNA polymerase Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  17. File list: DNS.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.05.AllAg.Leukemic_bone_marrow mm9 DNase-seq Blood Leukemic bone marrow http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  18. File list: Unc.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Leukemic_bone_marrow mm9 Unclassified Blood Leukemic bone marrow h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  19. File list: Oth.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Leukemic_bone_marrow mm9 TFs and others Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  20. File list: Pol.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Leukemic_bone_marrow mm9 RNA polymerase Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  1. File list: His.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Leukemic_bone_marrow mm9 Histone Blood Leukemic bone marrow SRX471...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  2. File list: ALL.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Leukemic_bone_marrow mm9 All antigens Blood Leukemic bone marrow S...243 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  3. File list: DNS.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.Leukemic_bone_marrow mm9 DNase-seq Blood Leukemic bone marrow http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  4. File list: Oth.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Leukemic_bone_marrow mm9 TFs and others Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  5. Bone marrow transplantation reverses new-onset immunoinflammatory diabetes in a mouse model.

    Science.gov (United States)

    Lv, Cheng-Lan; Wang, Jing; Xie, Ting; Ouyang, Jian

    2014-01-01

    Bone marrow transplantation might be an effective method to cure type 1 diabetes mellitus. This study aimed to investigate whether bone marrow transplantation could reverse hyperglycemia in diabetic mice and whether high-dose total body irradiation followed by high-dose bone marrow mononuclear cell infusion could improve the efficiency of bone marrow transplantation in treating diabetic mice. Diabetic mice after multiple low doses of streptozotocin injection were irradiated followed by infusion with approximately 1×10(7) bone marrow mononuclear cells intravenously. Before and after bone marrow transplantation, fasting blood glucose, intraperitoneal glucose tolerance test, serum insulin, pancreatic histology, and the examination of insulin and glucagon in islets were processed. All recipients returned to near euglycemic within 1 week after undergoing bone marrow transplantation. No mice became hyperglycemia again during investigation period. The change of serum insulin, glucose tolerance test, pancreatic histology and the expression of insulin and glucagon in recipient islets after bone marrow transplantation all revealed islets regeneration and significant amelioration when compared respectively with those of diabetic mice without bone marrow transplantation. Bone marrow transplantation contributed to reduce blood glucose, prevent further blood glucose hike in diabetic recipients, and promote islets regeneration. High-dose total body irradiation in combination with high-dose bone marrow monoclear cell infusion could improve the efficiency of bone marrow transplantation in treating streptozotocin-induced diabetes.

  6. Role of staging bone marrow examination in children with Hodgkin disease

    NARCIS (Netherlands)

    Mahoney, DH; Schreuders, LC; Gresik, MV; McClain, KL

    1998-01-01

    Purpose. To determine the value of bone marrow trephine biopsy as part of the clinical staging for children presenting with Hodgkin disease. Patients and Methods, A retrospective study of pre-treatment bone marrow examinations was undertaken to examine the value of bone marrow staging in children wi

  7. Primary bone marrow lymphoma: an uncommon extranodal presentation of aggressive non-hodgkin lymphomas.

    NARCIS (Netherlands)

    Martinez, A.; Ponzoni, M.; Agostinelli, C.; Hebeda, K.M.; Matutes, E.; Peccatori, J.; Campidelli, C.; Espinet, B.; Perea, G.; Acevedo, A.; Mehrjardi, A.Z.; Martinez-Bernal, M.; Gelemur, M.; Zucca, E.; Pileri, S.; Campo, E.; Lopez-Guillermo, A.; Rozman, M.

    2012-01-01

    Bone marrow involvement by lymphoma is considered a systemic dissemination of the disease arising elsewhere, although some tumors may arise primarily in the bone marrow microenvironment. Primary bone marrow lymphoma (PBML) is a rare entity whose real boundaries and clinicobiological significance are

  8. EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; KerryAtkinson

    1994-01-01

    We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo.IL-4 alone was found to be incapable of stimulating colony formation,but it inhibited both IL-3-and GM-CSF-induced colony for-mation by murine hematopoietic progenitor cells.In contrast,colony formation induced by G-CSF was enhanced in the presence of IL-4.We also studied the influence of IL-4 on hematopoietie reconstiution after allogeneic bone marrow transplantation in a murine model,and found that IL-4 and G-CSF was significantly suppressed by IL-4.The combination of IL-4 and GM-CSF caused a significant decrease in the absolute mumber of meutrophils.

  9. 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.

  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.

    2010-01-01

    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 g

  11. 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 m

  12. 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...

  13. Archival bone marrow samples: suitable for multiple biomarker analysis.

    Science.gov (United States)

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata; Landsem, Veslemøy M; Rasmussen, Kirsten K; Borst, Louise; Gupta, Ramneek; Schmiegelow, Kjeld; Klungland, Helge

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole genome amplification (WGA), multiple marker analysis including 10 short tandem repeats, and finally a comprehensive genotyping of 33,683 single nucleotide polymorphisms (SNPs) with multiplexed targeted next-generation sequencing. A total of 73 samples from 21 bone marrow smears and 13 bone marrow biopsies from 18 Danish and Norwegian childhood acute lymphoblastic leukemia patients were included and compared with corresponding blood samples. Samples were grouped according to the age of sample and whether WGA was performed or not. We found that measurements of DNA concentration after DNA extraction was dependent on detection method and that spectrophotometry overestimated DNA amount compared with fluorometry. In the short tandem repeat analysis, detection rate dropped slightly with longer fragments. After WGA, this drop was more pronounced. Samples stored for 0 to 3 years showed better results compared with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP analysis seems feasible, but the method has to be further optimized.

  14. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  15. Bone marrow failure syndromes and refractory cytopenia of childhood

    NARCIS (Netherlands)

    A.M. Aalbers (Anna Maartje)

    2014-01-01

    markdownabstract__Abstract__ Hematopoiesis, or blood cell production, is sustained through hematopoietic stem cells, which are self-renewing cells that reside in the bone marrow, and that are capable of producing daughter cells that proliferate and mature to provide all adult blood effector cells,

  16. A Role For Photodynamic Therapy In Autologous Bone Marrow Transplantation

    Science.gov (United States)

    Sieber, Fritz

    1988-02-01

    Simultaneous exposure to the amphipathic fluorescent dye merocyanine 540 (MC 540) and light of a suitable wavelength rapidly kills leukemia, lymphoma, and neuroblastoma cells but spares normal pluripotent hematopoietic stem cells. Tests in several preclinical models and early results of a phase I clinical trial suggest that MC 540-mediated photosensitization may be useful for the extracorporeal purging of autologous remission bone marrow grafts.

  17. Therapy Effects of Bone Marrow Stromal Cells on Ischemic Stroke

    OpenAIRE

    Xinchun Ye; Jinxia Hu; Guiyun Cui

    2016-01-01

    Stroke is the second most common cause of death and major cause of disability worldwide. Recently, bone marrow stromal cells (BMSCs) have been shown to improve functional outcome after stroke. In this review, we will focus on the protective effects of BMSCs on ischemic brain and the relative molecular mechanisms underlying the protective effects of BMSCs on stroke.

  18. Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.

    Directory of Open Access Journals (Sweden)

    Alexandra Berger

    Full Text Available Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/- showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-, Tac4 (-/- and Tac1 (-/-/Tac4 (-/- mice repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.

  19. SPONTANEOUS TRANSFORMATION OF CULTURED PORCINE BONE MARROW STROMAL CELLS

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Li, Haisheng;

    INTRODUCTION Recently, the possibility that tumors originate from cancer stem cells (CSCs) has been proposed. Stem cells and CSCs share certain features such as self-renewal and differentiation potential. The aim of this study was to evaluate whether bone marrow stromal cells (BMSC) after long-te...

  20. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    Science.gov (United States)

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc.

  1. Oncostatin M maintains the hematopoietic microenvironment in the bone marrow by modulating adipogenesis and osteogenesis.

    Directory of Open Access Journals (Sweden)

    Fumi Sato

    Full Text Available The bone marrow (BM is an essential organ for hematopoiesis in adult, in which proliferation and differentiation of hematopoietic stem/progenitor cells (HSPC is orchestrated by various stromal cells. Alterations of BM hematopoietic environment lead to various hematopoietic disorders as exemplified by the linking of fatty marrow with increased adipogenesis to anemia or pancytopenia. Therefore, the composition of mesenchymal stromal cell (MSC-derived cells in the BM could be crucial for proper hematopoiesis, but the mechanisms underlying the MSC differentiation for hematopoiesis remain poorly understood. In this study, we show that Oncostatin M (OSM knock out mice exhibited pancytopenia advancing fatty marrow with age. OSM strongly inhibited adipogenesis from BM MSC in vitro, whereas it enhanced their osteogenesis but suppressed the terminal differentiation. Intriguingly, OSM allowed the MSC-derived cells to support the ex vivo expansion of HSPC effectively as feeder cells. Furthermore, the administration of OSM in lethally irradiated wild-type mice blocked fatty marrow and enhanced the recovery of HSPC number in the BM and peripheral blood cells after engraftment of HSPC. Collectively, OSM plays multiple critical roles in the maintenance and development of the hematopoietic microenvironment in the BM at a steady state as well as after injury.

  2. 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.

  3. Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

    Directory of Open Access Journals (Sweden)

    Bechtold Astrid

    2007-01-01

    Full Text Available Abstract Background DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4. The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. Methods We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4 deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT using a fludarabine-based conditioning regimen without irradiation. Results The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. Conclusion HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor.

  4. 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 vascu

  5. Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets

    Institute of Scientific and Technical Information of China (English)

    Naoaki; Sakata; Nathaniel; K; Chan; John; Chrisler; Andre; Obenaus; Eba; Hathout

    2010-01-01

    AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nerve...

  6. Stem cell niche failure concerns bone marrow failure--a diagnostic and therapeutic consideration.

    Science.gov (United States)

    Law, Sujata; Chaudhuri, Samaresh

    2011-01-01

    Diseases of the bone marrow often referred to as "Bone marrow failure" have complicated pathophysiological picture with respect to hematopoietic systemic function. The reason for such bone marrow disorder is not well understood till date, although some sporadic etiological sources have been described earlier. With the advent of current investigations, hematopoietic stem cell involvement together with the failure of signaling interaction within the bone marrow niche has been found to reveal interesting correlations with the disease onset. The present review furnishes justification for bone marrow failure as a concern of stem cell niche failure and hints at providing important clues for disease diagnosis and therapeutic maneuver.

  7. 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)

  8. Bone marrow MR imaging findings in disuse osteoporosis

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Marcelo R. de [Hospital Mae de Deus, Porto Alegre (Brazil); Wesselly, Michelle; Chung, Christine B.; Resnick, Donald [University of California, San Diego, CA (United States)

    2011-05-15

    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.)

  9. 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.

  10. 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.

  11. Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    2012-12-01

    Full Text Available Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate liga­ment (ACL reconstruction. The periosteum contains osteochondral progenitor cells that can differenti­ate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaf­fold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fi­brin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical as­say and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was ob­served. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposi­tion with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochon­dral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengi­neered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to en­hance tendon-bone junction healing.

  12. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. The topologic and chronologic patterns of hematopoietic cell seeding in host femoral bone marrow after transplantation.

    Science.gov (United States)

    Askenasy, Nadir; Stein, Jeremiah; Yaniv, Isaac; Farkas, Daniel L

    2003-08-01

    The early stages of homing, seeding, and engraftment of hematopoietic stem and progenitor cells are poorly characterized. We have developed an optical technique that allows in vivo tracking of transplanted, fluorescent-tagged cells in the host femurs. In this study we used fluorescence microscopy to monitor the topologic and chronologic patterns of hematopoietic cell seeding in the femoral bone marrow (BM) of mice. PKH-labeled cells homed to the femur within minutes after injection into a peripheral vein. Most cells drifted within the marrow space and gradually seeded in clusters close to the endosteal surface of the epiphyseal cortex. Three days after transplantation 85% to 94% (14%) of PKH-labeled cells in the femoral marrow were located within 100 microm of the epiphyseal bone surface (P <.001 versus the more central cells), whereas labeled cells were absent in the femoral diaphysis. Primary seeding of juxtaendosteal, epiphyseal marrow occurred independently of recipient conditioning (myeloablated and nonconditioned hosts), donor-recipient antigen disparity, or the phenotype of the injected cells (whole BM and lineage-negative cells) and was consistently observed in secondary recipients of BM-homed cells. Seeding in regions close to the epiphyseal bone was also observed in freshly excised femurs perfused ex vivo and in femurs assessed without prior placement of optical windows, indicating that the site of primary seeding was not affected by surgical placement of optical windows. Four to 5 days after transplantation, cellular clusters appeared in the more central regions of the epiphyses and in the diaphyses. Centrally located cells showed decreased PKH fluorescence, suggesting that they were progeny of the seeding cells, and brightly fluorescent cells (quiescent first-generation seeding cells) were observed close to the bone surface for as long as 24 days after transplantation. These data indicate that the periphery of the femoral marrow hosts primary seeding

  14. Bone marrow biopsy findings in brucellosis patients with hematologic abnormalities

    Institute of Scientific and Technical Information of China (English)

    Cengiz Demir; Mustafa Kasim Karahocagil; Ramazan Esen; Murat Atmaca; Hayriye G(o)nüllü; Hayrettin Akdeniz

    2012-01-01

    Background Brucellosis can mimic various multisytem diseases,showing wide clinical polymorphism that frequently leads to misdiagnosis and treatment delay,further increasing the complication rates.In this study,we aimed to examine bone marrow biopsy findings in brucellosis cases presenting with hematologic abnormalities.Methods Forty-eight brucellosis cases were prospectively investigated.Complaints and physical examination findings of patients were recorded.Patients' complete blood count,routine biochemical tests,erythrocyte sedimentation rate,C-reactive protein and serological screenings were performed.Bone marrow biopsy and aspiration was performed in patients with cytopenia,for bone marrow examination and brucella culture,in accordance with the standard procedures from spina iliaca posterior superior region of pelvic bone.Results Of the 48 patients,35 (73%) were female and 13 (27%) were male.Mean age was (34.8±15.4) years (age range:15-70 years).Anemia,leukopenia,thrombocytopenia and pancytopenia were found in 39 (81%),28 (58%),22 (46%) and 10 patients (21%),respectively.In the examination of bone marrow,hypercellularity was found In 35 (73%) patients.Increased megacariocytic,erythroid and granulocytic series were found in 28 (58%),15 (31%) and 5 (10%) patients,respectively.In addition,hemophagocytosis was observed in 15 (31%) patients,granuloma observed in 12 (25%) and increased eosinophil and plasma cells observed in 9 (19%) patients.Conclusion According to the results of our series,hemophagocytosis,microgranuloma formation and hypersplenism may be responsible for hematologic complications of brucellosis.

  15. 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.

  16. [Effect of continuous gamma-radiation at low doses on clonogenic hemopoietic (CFU-S) and stromal (CFU-F) bone marrow cells ].

    Science.gov (United States)

    Domaratskaia, E I; Starostin, V I; Tsetlin, V V; Butorina, N N; Bueverova, E I; Bragina, E V; Khrushchov, N G

    2002-01-01

    We studied the effects of low doses of continuous gamma-irradiation (Co60, 10 days, mean daily dose power 1.5-2.0 mGy, total dose 15 mGy) on hemopoietic and stromal progenitor cells of murine bone marrow. The content of hemopoietic clonogenic cells representing a "younger" (CFU-S-11) and more "mature" (CFU-S-7) categories in the compartment of stem cells was determined in the bone marrow. The state of bone marrow stroma was estimated by the method of in vitro cloning according to the number of progenitor cells that form colonies of fibroblasts (CFU-F) and by the method of ectopic transplantation according to the capacity of stroma of organizing and building new hemopoietic territories. Continuous gamma-irradiation at low doses, that were by one order of magnitude lower than those inducing hermesis, exerted a stimulating effect on both hemopoietic (CFU-S) and stromal (CFU-F) progenitor cells. The number of CFU-S in the compartment of stem cells of the bone marrow markedly increased and they formed larger hemopoietic territories but these cells appeared to create a qualitatively different microenvironment, which stimulated the proliferation of CFU-S.

  17. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    Science.gov (United States)

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  18. In Vivo Osteoinductive Effect and In Vitro Isolation and Cultivation Bone Marrow Mesenchymal Stem Cells

    OpenAIRE

    Redžić, Amira; Smajilagić, Amer; Aljičević, Mufida; Berberović, Ljubomir

    2010-01-01

    Bone marrow contains cell type termed Mesenchymal Stem Cells (MSC), first recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That MSCs have potential to differentiate in vitro in to the various cells lines as osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study were to show in vivo capacity of bone marrow MSC to produce bone in surgically created non critical size mandible defects New Zeeland Rabbits, and then in second part of study to iso...

  19. Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

    OpenAIRE

    2011-01-01

    Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazo...

  20. Evidence of Receptor-Mediated Elimination of Erythropoietin by Analysis of Erythropoietin Receptor mRNA Expression in Bone Marrow and Erythropoietin Clearance During Anemia

    OpenAIRE

    Nalbant, Demet; SALEH, Mohammad; Goldman, Frederic D.; Widness, John A.; Veng-Pedersen, Peter

    2010-01-01

    Erythropoietin (Epo) is the primary hormone that stimulates erythroid proliferation and differentiation through its cell surface receptor (EpoR) on erythroid progenitor cells. Previous studies have suggested that the bone marrow plays an important role in Epo's elimination. The changes in the EpoR mRNA levels and Epo's clearance in the bone marrow of 11 newborn lambs were studied to elucidate the role of EpoR in Epo's clearance under anemic conditions. Epo mRNA levels were measured by real-ti...

  1. 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.

  2. 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.

  3. 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.

  4. 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 of a var......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...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  5. Bone Marrow Stem Cell as a Potential Treatment for Diabetes

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Diabetes mellitus (DM is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs and tissue stem cells (TSCs to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.

  6. Differentiation of Bone Marrow Mesenchymal Cells to Neural Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To explore the possibility and condition of differentiation of bone marrow mesenchymal cells (BMSCs) to neural cells in vitro, BMSCs from whole bone marrow of rats were cultured. The BMSCs of passage 3 were identified with immunocytochemical staining of CD44 ( + ), CD71 ( + )and CD45(-). There were type Ⅰ and type Ⅱ cells in BMSCs. Type Ⅰ BMSCs were spindleshaped and strong positive in immunocytochemical staining of CD44 and CD71, whereas flat and big type Ⅱ BMSCs were lightly stained. The BMSCs of same passage were induced to differentiate into neural cells by β-mercaptoethanol (BME). After induction by BME, the type Ⅰ BMSCs withdrew to form neuron-like round soma and axon-like and dendrite-like processes, and were stained positively for neurofilament (NF). The type Ⅱ BMSCs did not change in the BME medium and were negatively or slightly stained of NF.

  7. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.;

    2015-01-01

    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......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...

  8. Bone marrow transplantation at the University of Nebraska Medical Center.

    Science.gov (United States)

    Bierman, P J; Armitage, J O

    1993-08-01

    The bone marrow transplant program at UNMC is currently one of the most active programs in the country. The benefits to patients who are cured of disease by transplantation cannot be measured. The large volume of clinical and basic science research related to transplantation has enhanced the academic stature of UNMC. The combination of patient care, education, clinical research, and basic science research provides an excellent model for the operation of an academic medical institution.

  9. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    Science.gov (United States)

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  10. Occupational therapy and the pediatric division of bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Thais Clemente Idemori

    2016-04-01

    Full Text Available Introduction: Bone Marrow Transplantation may cause a series of restrictions to patients. The child’s illness and hospitalization may further change daily life activities, playing and school routine; and social interaction, which will interfere in occupational roles. The occupational therapy procedures seek to provide a more accessible experience in hospital concerning the possibilities of involvement, favoring the child’s development through activities. Objective: This study aimed to describe the practice of an occupational therapist during therapeutic process with a school age child who has undergone bone marrow transplantation. Method: This is a qualitative research with a case study approach. Data was collected with a short form of personal and professional identification and characterization, and a semi-structured interview script. The interview was fully transcribed, and analyzed under the content analysis overview. Through the content obtained in the interviews, it was possible to raise four categories: occupational roles affected by illness, hospitalization; occupational therapy processes; benefits to children by the occupational therapy activities; and, successful practices: essential factors and theoretical principles. Results: The results showed that the occupational therapist took on roles as mediator between the hospital and the child’s original environment, and the relations to family, hospital team, towards the child’s needs and his/her life experience (school, family, hospital. Conclusion: It is expected that this study may contribute to the knowledge and propagation of the practice being developed by the therapists in children with bone marrow transplantation.

  11. 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.

  12. Bone marrow leishmaniasis: a review of situation in Thailand.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2011-10-01

    Leishmaniasis is an important tropical vector-borne disease. This infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. The general situation of the leishmaniasis in Thailand is hereby reviewed. Although Thailand is a tropical country, the leishmaniasis is not endemic but sporadic. The imported cases are documented in some literatures. The serious form of leishmaniasis, the visceral leishmaniasis is also detectable in Thailand. Also, the author performed an in depth literature review of the reports of bone marrow leishmaniasis, a specific kind of visceral leishmaniasis, in Thailand in order to summarize the characteristics of this infection among Thai patients. According to this review, there have been at least 5 reports in the literature of 6 cases of bone marrow leishmaniasis in the Thai population, of which no case was lethal. Concerning the clinical manifestations, all except had prolonged fever with unknown origin. From physical examination, all had hepatosplenomegaly. The striking findings were active hemophagocytosis with increased proliferation of lymphoidplasma cell line in the bone marrow and amastigotes of Leishmania donovani was demonstrated. Considering the treatment, pantavalent antimony compound was used and the excellent improvement and complete recovery. Finally, the author also discussed on the importance of leishmaniasis in Thailand relating to the present globalization and good traveling system.

  13. [Effect of aclacinomycin A on bone marrow (author's transl)].

    Science.gov (United States)

    Ohmori, K; Shirai, M; Kiyosaki, T; Hori, S; Tone, H

    1980-04-01

    Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.

  14. Hematopoietic progenitor migration to the adult thymus

    OpenAIRE

    Zlotoff, Daniel A.; Bhandoola, Avinash

    2011-01-01

    While most hematopoietic lineages develop in the bone marrow (BM), T cells uniquely complete their development in the specialized environment of the thymus. Hematopoietic stem cells with long-term self-renewal capacity are not present in the thymus. As a result, continuous T cell development requires that BM-derived progenitors be imported into the thymus throughout adult life. The process of thymic homing begins with the mobilization of progenitors out of the bone marrow, continues with thei...

  15. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Xuming Hua; Fang Hua; Wenwei Mao; Liang Wan; Shiting Li

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

  16. Differentiation of rat bone marrow stem cells in liver after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Yu-Tao Zhan; Yu Wang; Lai Wei; Bin Liu; Hong-Song Chen; Xu Cong; Ran Fei

    2006-01-01

    AIM: To investigate the differentiation of rat bone marrow stem cells in liver after partial hepatectomy.METHODS: Bone marrow cells were collected from the tibia of rat with partial hepatectomy, the medial and left hepatic lobes were excised. The bone marrow stem cells (Thy+CD3-CD45RA- cells) were enriched from the bone marrow cells by depleting red cells and fluorescence-activated cell sorting. The sorted bone marrow stem cells were labeled by PKH26-GL in vitro and autotransplanted by portal vein injection. After 2wk, the transplanted bone marrow stem cells in liver were examined by the immunohistochemistry of albumin (hepatocyte-specific marker).RESULTS: The bone marrow stem cells (Thy+CD3-CD45RA- cells) accounted for 2.8% of bone marrow cells without red cells. The labeling rate of 10μM PKH26-GL on sorted bone marrow stem cells was about 95%.There were sporadic PKH26-GL-labeled cells among hepatocytes in liver tissue section, and some of the cells expressed albumin.CONCLUSION: Rat bone marrow stem cells can differentiate into hepatocytes in regenerative environment and may participate in liver regeneration after partial hepatectomy.

  17. Use of autologous bone marrow mononuclear cells and cultured bone marrow stromal cells in dogs with orthopaedic lesions.

    Science.gov (United States)

    Crovace, A; Favia, A; Lacitignola, L; Di Comite, M S; Staffieri, F; Francioso, E

    2008-09-01

    The aim of the study is to evaluate the clinical application in veterinary orthopedics of bone marrow mononuclear cells (BMMNCs) and cultured bone marrow stromal cells (cBMSCs) for the treatment of some orthopaedic lesions in the dog. The authors carried out a clinical study on 14 dogs of different breed, age and size with the following lesions: 1 bone cyst of the glenoid rime; 2 nonunion of the tibia; 3 nonunion of the femur; 2 lengthening of the radius; 1 large bone defect of the distal radius;1 nonunion with carpus valgus; 4 Legg-Calvé-Perthés disease. In 9 cases the BMMCNs were used in combination with a three dimensional resorbable osteogenic scaffold the chemical composition and size of which facilitates the ingrowth of bone. In these cases the BMMNCs were suspended in an adequate amount of fibrin glue and then distribuited uniformly on a Tricalcium-Phosphate (TCP) scaffold onto which were also added some drops of thrombin. In 1 case of nonunion of the tibia and in 3 cases of Legg-Calvè-Perthés (LCP) disease the cultured BMSCs were used instead because of the small size of the dogs and of the little amount of aspirated bone marrow. X-ray examinations were performed immediately after the surgery. Clinical, ultrasounds and X-ray examinations were performed after 20 days and then every month. Until now the treated dogs have shown very good clinical and X-ray results. One of the objectives of the study was to use the BMMNCs in clinical application in orthopaedic lesions in the dog. The advantages of using the cells immediately after the bone marrow is collected, are that the surgery can be performed the same day, the cells do not need to be expanded in vitro, they preserve their osteogenic potential to form bone and promote the proper integration of the implant with the bone and lastly, the technique is easier and the costs are lower.

  18. Modulation of Selectin-Mediated Adhesion of Flowing Lymphoma and Bone Marrow Cells by Immobilized SDF-1

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Hedges

    2014-08-01

    Full Text Available The α-chemokine, stromal-derived factor-1 (SDF-1, has been linked to the homing of circulating tumor cells to bone. SDF-1 is expressed by bone microvascular cells and osteoblasts and normally functions to attract blood-borne hematopoietic stem and progenitor cells to marrow. It has been shown that treatment of cancer cells with soluble SDF-1 results in a more aggressive phenotype; however, the relevance of the administration of the soluble protein is unclear. As such, a flow device was functionalized with P-selectin and SDF-1 to mimic the bone marrow microvasculature and the initial steps of cell adhesion. The introduction of SDF-1 onto the adhesive surface was found to significantly enhance the adhesion of lymphoma cells, as well as low-density bone marrow cells (LDBMC, both in terms of the number of adherent cells and the strength of cell adhesion. Thus, SDF-1 has a synergistic effect with P-selectin on cancer cell adhesion and may be sufficient to promote preferential metastasis to bone.

  19. 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.).

  20. 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.

  1. Use of osmium tetroxide staining with microcomputerized tomography to visualize and quantify bone marrow adipose tissue in vivo.

    Science.gov (United States)

    Scheller, Erica L; Troiano, Nancy; Vanhoutan, Joshua N; Bouxsein, Mary A; Fretz, Jackie A; Xi, Yougen; Nelson, Tracy; Katz, Griffin; Berry, Ryan; Church, Christopher D; Doucette, Casey R; Rodeheffer, Matthew S; Macdougald, Ormond A; Rosen, Clifford J; Horowitz, Mark C

    2014-01-01

    Adipocytes reside in discrete, well-defined depots throughout the body. In addition to mature adipocytes, white adipose tissue depots are composed of many cell types, including macrophages, endothelial cells, fibroblasts, and stromal cells, which together are referred to as the stromal vascular fraction (SVF). The SVF also contains adipocyte progenitors that give rise to mature adipocytes in those depots. Marrow adipose tissue (MAT) or marrow fat has long been known to be present in bone marrow (BM) but its origin, development, and function remain largely unknown. Clinically, increased MAT is associated with age, metabolic diseases, drug treatment, and marrow recovery in children receiving radiation and chemotherapy. In contrast to the other depots, MAT is unevenly distributed in the BM of long bones. Conventional quantitation relies on sectioning of the bone to overcome issues with distribution but is time-consuming, resource intensive, inconsistent between laboratories and may be unreliable as it may miss changes in MAT volume. Thus, the inability to quantitate MAT in a rapid, systematic, and reproducible manner has hampered a full understanding of its development and function. In this chapter, we describe a new technique that couples histochemical staining of lipid using osmium tetroxide with microcomputerized tomography to visualize and quantitate MAT within the medullary canal in three dimensions. Imaging of osmium staining provides a high-resolution map of existing and developing MAT in the BM. Because this method is simple, reproducible, and quantitative, we expect it will become a useful tool for the precise characterization of MAT.

  2. Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes.

    Science.gov (United States)

    Huan, J; Hornick, N I; Goloviznina, N A; Kamimae-Lanning, A N; David, L L; Wilmarth, P A; Mori, T; Chevillet, J R; Narla, A; Roberts, C T; Loriaux, M M; Chang, B H; Kurre, P

    2015-12-01

    We recently demonstrated that acute myeloid leukemia (AML) cell lines and patient-derived blasts release exosomes that carry RNA and protein; following an in vitro transfer, AML exosomes produce proangiogenic changes in bystander cells. We reasoned that paracrine exosome trafficking may have a broader role in shaping the leukemic niche. In a series of in vitro studies and murine xenografts, we demonstrate that AML exosomes downregulate critical retention factors (Scf, Cxcl12) in stromal cells, leading to hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow. Exosome trafficking also regulates HSPC directly, and we demonstrate declining clonogenicity, loss of CXCR4 and c-Kit expression, and the consistent repression of several hematopoietic transcription factors, including c-Myb, Cebp-β and Hoxa-9. Additional experiments using a model of extramedullary AML or direct intrafemoral injection of purified exosomes reveal that the erosion of HSPC function can occur independent of direct cell-cell contact with leukemia cells. Finally, using a novel multiplex proteomics technique, we identified candidate pathways involved in the direct exosome-mediated modulation of HSPC function. In aggregate, this work suggests that AML exosomes participate in the suppression of residual hematopoietic function that precedes widespread leukemic invasion of the bone marrow directly and indirectly via stromal components.

  3. 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.

  4. Dexamethasone-Induced Oxidative Stress Enhances Myeloma Cell Radiosensitization While Sparing Normal Bone Marrow Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Soumen Bera

    2010-12-01

    Full Text Available Dexamethasone (Dex and radiation therapy are established modalities in multiple myeloma. In this study, we propose a novel combination of Dex plus radiation that shows superior clonogenic cell killing and apoptosis of myeloma cells and selectively eliminates myeloma cells when cocultured with bone marrow stromal cells (BMSCs. Dex was found to inhibit the release of interleukin-6 from irradiated BMSCs, which is an established myeloma cell proproliferative cytokine. In 5TGM1 model, the combination of Dex with skeletal targeted radiotherapy (153-Sm-EDTMP prolonged median survival time and inhibited radiation-induced myelosuppression. A two-cycle treatment of Dex plus 153-Sm-EDTMP was well tolerated and further improved median survival time. Mechanistically, Dex increased superoxide and hydrogen peroxide production and augmented radiation-induced oxidative stress and cell death of myeloma cells. In contrast, Dex inhibited radiation-induced increase in pro-oxidant levels and enhanced the clonogenic survival in normal hematopoietic stem and progenitor cells. Treatment with either N-acetylcysteine or the combination of polyethylene glycol (PEG-conjugated copper, zinc-superoxide dismutase, and PEG-catalase significantly protected myeloma cells from Dex-induced clonogenic death. Overall, these results demonstrate that Dex in combination with radiotherapy enhances the killing of myeloma cells while protecting normal bone marrow hematopoiesis through a mechanism that involves selective increases in oxidative stress.

  5. Differentiation of mouse bone marrow derived stem cells toward microglia-like cells

    Directory of Open Access Journals (Sweden)

    Stolzing Alexandra

    2011-08-01

    Full Text Available Abstract Background Microglia, the macrophages of the brain, have been implicated in the causes of neurodegenerative diseases and display a loss of function during aging. Throughout life, microglia are replenished by limited proliferation of resident microglial cells. Replenishment by bone marrow-derived progenitor cells is still under debate. In this context, we investigated the differentiation of mouse microglia from bone marrow (BM stem cells. Furthermore, we looked at the effects of FMS-like tyrosine kinase 3 ligand (Flt3L, astrocyte-conditioned medium (ACM and GM-CSF on the differentiation to microglia-like cells. Methods We assessed in vitro-derived microglia differentiation by marker expression (CD11b/CD45, F4/80, but also for the first time for functional performance (phagocytosis, oxidative burst and in situ migration into living brain tissue. Integration, survival and migration were assessed in organotypic brain slices. Results The cells differentiated from mouse BM show function, markers and morphology of primary microglia and migrate into living brain tissue. Flt3L displays a negative effect on differentiation while GM-CSF enhances differentiation. Conclusion We conclude that in vitro-derived microglia are the phenotypic and functional equivalents to primary microglia and could be used in cell therapy.

  6. In vitro characterization of bone marrow stromal cells from osteoarthritic donors

    DEFF Research Database (Denmark)

    Stiehler, Maik; Rauh, Juliane; Bünger, Cody;

    2016-01-01

    BMSCs, also known as bone marrow-derived mesenchymal stem cells, provide an excellent source of progenitor cells for regenerative therapy. To assess whether osteoarthritis (OA) affects the regenerative potential of BMSCs we compared the proliferation and differentiation potential as well......-forming-units of fibroblastsmax (CFU-F) assay. Differentiation assays included immunohistology, cell-specific alkaline phosphatase (ALP) activity, and osteogenic, chondrogenic as well as adipogenic marker gene qRT-PCR. Expression of BMSC-associated surface markers was analyzed using flow cytometry. No significant intergroup...... differences were observed concerning the proliferation potential, cell-specific ALP activity as well as adipogenic and osteogenic differentiation marker gene expressions. Interestingly, SOX9 gene expression levels were significantly increased in OA-BMSCs after 14days of chondrogenic stimulation (p

  7. Parathyroid hormone administration improves bone marrow microenvironment and partially rescues haematopoietic defects in Bmi1-null mice.

    Directory of Open Access Journals (Sweden)

    Ruinan Lu

    Full Text Available The epigenetic regulator Bmi1 is key in haematopoietic stem cells, and its inactivation leads to defects in haematopoiesis. Parathyroid hormone (PTH, an important modulator of bone homeostasis, also regulates haematopoiesis, so we asked whether PTH administration improves bone marrow microenvironment and rescues the haematopoietic defects in Bmi1-null mice. The mice were treated with PTH1-34 (containing the first 34 residues of mature PTH, an anabolic drug currently used for treating osteoporosis, and compared with the vehicle-treated Bmi1-/- and wild-type littermates in terms of skeletal and haematopoietic phenotypes. We found that the administration significantly increased all parameters related to osteoblastic bone formation and significantly reduced the adipocyte number and PPARγ expression. The bone marrow cellularity, numbers of haematopoietic progenitors and stem cells in the femur, and numbers of lymphocytes and other white blood cells in the peripheral blood all increased significantly when compared to vehicle-treated Bmi1-/- mice. Moreover, the number of Jagged1-positive cells and percentage of Notch intracellular domain-positive bone marrow cells and protein expression levels of Jagged1 and NICD in bone tissue were also increased in Bmi1-/- mice upon PTH1-34 administration,whereas the up-regulation of PTH on both Notch1 and Jagged1 gene expression was blocked by the Notch inhibitor DAPT administration. These results thus indicate that PTH administration activates the notch pathway and partially rescues haematopoietic defects in Bmi1-null mice, further suggesting that haematopoietic defects in the animals are not only a result of reduced self-renewal of haematopoietic stem cells but also due to impaired bone marrow microenvironment.

  8. ENRICHMENT AND CHARACTERIZATION OF THYMUS-REPOPULATING CELLS IN STROMA-DEPENDENT CULTURES OF RAT BONE-MARROW

    NARCIS (Netherlands)

    PRAKAPAS, Z; DENOYELLE, M; DARGEMONT, C; KROESE, FGM; THIERY, JP; DEUGNIER, MA

    1993-01-01

    The bone marrow precursor cells seeding the thymus have been difficult to investigate using fresh bone marrow and in vivo thymus reconstitution assays. We have therefore designed a short-term bone marrow culture system allowing the study of thymus-repopulating cells in the marrow microenvironment. L

  9. Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Fariba Rezaee

    Full Text Available BACKGROUND: The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC. As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we investigated BMSC neurotrophin receptor expression by flow cytometric analysis to determine differences in expression as well as potential to respond to NGF or BDNF. Intracellular signaling subsequent to neurotrophin stimulation of BMSC was analyzed by western blot, microarray analysis, confocal microscopy and real-time PCR. Analysis of BMSC Interleukin-6 (IL-6 expression was completed using ELISA and real-time PCR. CONCLUSION: BMSC established from different individuals had distinct expression profiles of the neurotrophin receptors, TrkA, TrkB, TrkC, and p75(NTR. These receptors were functional, demonstrated by an increase in Akt-phosphorylation following BMSC exposure to recombinant NGF or BDNF. Neurotrophin stimulation of BMSC resulted in increased IL-6 gene and protein expression which required activation of ERK and p38 MAPK signaling, but was not mediated by the NFkappaB pathway. BMSC response to neurotrophins, including the up-regulation of IL-6, may alter their support of hematopoiesis and regulate the availability of inflammatory cells for migration to sites of injury or infection. As such, these studies are relevant to the growing appreciation of the interplay between neurotropic mediators and the regulation of hematopoiesis.

  10. The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

    Science.gov (United States)

    Parkman, Robertson

    1986-06-01

    Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

  11. 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.

  12. Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow aplasia mouse model: A study to explore the novel mechanism of pesticide toxicity.

    Science.gov (United States)

    Chattopadhyay, Sukalpa; Chatterjee, Ritam; Law, Sujata

    2016-10-01

    According to case-control studies, long-term pesticide exposure can cause bone marrow aplasia like hematopoietic degenerative disease leading to impaired hematopoiesis and increased risk of aplastic anemia in human subjects. However, the exact mechanism of pesticide mediated hematotoxicity still remains elusive. In this study, we investigated the role of noncanonical Wnt signaling pathway, a crucial regulator of adult hematopoiesis, in pesticide induced bone marrow aplasia mouse model. Aplasia mouse model was developed following inhalation and dermal exposure of 5% aqueous mixture of common agriculturally used pesticides for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis and flowcytometric expression analysis of noncanonical Wnt signaling components, such as Wnt 5a, fzd5, NFAT, IFN-γ, intracellular Ca(2+) level were evaluated in the bone marrow hematopoietic stem/progenitor compartment of the control and pesticide induced aplasia groups of animals. Results showed that pesticide exposed mice were anemic with peripheral blood pancytopenia, hypocellular degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon pesticide exposure, Wnt 5a expression was severely downregulated with a decline in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp downregulation of NFATc2 transcription factor expression, the major target of pesticide toxicity and its target molecule IFN-γ. Taken together, our result suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the hematopoietic stem/progenitor compartment plays a crucial role behind the pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive hematopoietic stem cells' ability to maintain hematopoietic homeostasis and reconstitution mechanism in vivo during xenobiotic stress leading to ineffective hematopoiesis and evolution of bone marrow aplasia.

  13. Factors that influence Greeks' decision to register as potential bone marrow donors.

    Science.gov (United States)

    Galanis, P A; Sparos, L D; Katostaras, T; Velonakis, E; Kalokerinou, A

    2008-06-01

    Hemopoietic stem cells can be used from bone marrow or blood or umbilical cord blood of matched siblings or appropriately matched unrelated volunteers. Today, large bone marrow registries have been established to help identify volunteer unrelated bone marrow donors for patients lacking a family donor. Despite there being almost 10 million registered potential bone marrow donors (PBMD) worldwide, only 50% of white patients have a suitable bone marrow match. Growth in the number of PBMD increases the likelihood of finding a compatible donor for a patient. The attitudes and knowledge of 250 registered PBMD and 315 not registered PBMD toward bone marrow donation, tissues and organs donation, and blood donation were surveyed, using a questionnaire with 27 items. Multivariate logistic regression identified gender (females more often than males), regular blood donation, having a relative or a friend who has already been registered as PBMD, having a relative or a friend who needs bone marrow transplantation, family discussion about tissue and organ donation, knowledge about bone marrow transplantation, information about bone marrow transplantation, and trust in health professionals were independent predictive factors influencing people's decision to register as PBMD. Knowledge of these factors is important to target recruitment efforts.

  14. Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

    Science.gov (United States)

    Xin, Junping; Breslin, Peter; Wei, Wei; Li, Jing; Gutierrez, Rafael; Cannova, Joseph; Ni, Allen; Ng, Grace; Schmidt, Rachel; Chen, Haiyan; Parini, Vamsi; Kuo, Paul C.; Kini, Ameet R.; Stiff, Patrick; Zhu, Jiang; Zhang, Jiwang

    2017-01-01

    Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3. Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure. PMID:27634200

  15. 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.

  16. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    Science.gov (United States)

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.

  17. A stepwise procedure for isolation of murine bone marrow and generation of dendritic cells

    Directory of Open Access Journals (Sweden)

    Alka Madaan

    2014-02-01

    Full Text Available Bone marrow derived Dendritic cells (BMDCs are routinely employed in cell based assays to evaluate immunomodulatory and anti-inflammatory activities. Hence, simplified, stepwise, defined and standardized methods are required for isolation of bone marrow cells from mice, propagating them in presence of growth factors and obtaining high and reproducible yields of BMDCs. Here, we describe a detailed, stepwise protocol with pictorial representation to isolate bone marrow from mouse femur and development of dendritic cells. Mouse bone marrow cells are cultured in presence of granulocyte-macrophage colony stimulating factor (GM-CSF for 6 days to generate BMDCs.

  18. 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.

  19. Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

    Science.gov (United States)

    Cavallo, C; Desando, G; Ferrari, A; Zini, N; Mariani, E; Grigolo, B

    2016-01-01

    Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins.

  20. 糖尿病视网膜病变大鼠骨髓内皮祖细胞数量和功能变化%Change in the number and function of endothelial progenitor cells from the bone marrow of rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    张惟; 韩琪; 陈松; 颜华

    2013-01-01

    排列紊乱,细胞核肿胀、体积增大,DM6组视网膜厚度更薄,细胞排列紊乱更加明显,部分血管扩张.VEGF在CON组大鼠视网膜中表达为阴性,DM1组阳性率为(18.6±2.74)%,DM3组阳性率约为(34.3±2.21)%,DM6组阳性率为(58.73±2.48)%.结论 糖尿病大鼠骨髓EPCs数量较正常大鼠降低,生物学功能减退.随着DR的进展,EPCs数量逐渐回升.%Objective To observe the change in the number and function of endothelial progenitor cells (EPCs) from bone marrow in rats with diabetic retinopathy (DR); to discuss the role of EPCs in the pathogenesis of DR.Methods In an experimental study,50 male Wistar rats were divided into a control (CON) group (14 rats) and diabetes (DM) group (36 rats).The rats in the DM were further divided into 3 groups of 12 rats each based on the time periods when analysis was performed:1 month (DM1),3 months (DM3) and 6 months (DM6).Mononuclear cells were collected by density gradient centrifugation from the bone marrow of the rats.The isolated cells were cultivated in dishes coated with fibronectin.Immunofluorescence staining and flow cytometry were used to identify EPCs.The number of EPCs in the colony was assayed by CFU counting; proliferation,migration and adhesion function of EPCs were assayed by MTT chromatometry,modified Boyden chamber assay and adhesion activity assay.All eyeballs were examined by hematoxylin and eosin (HE) staining and vascular endothelial growth factor (VEGF) by immunity set expression.The correlation between changes in EPCs and DR morphological changes was analyzed.The changes in the number and function of EPCs from bone marrow and expression of VEGF in the retina were analyzed by single factor analysis of variance and LSD-t test.Results The number of cell clusters in bone marrow-derived EPCs was significantly reduced in the DM1,DM3,DM6 groups (9.6±1.8,11.5±2.5,14.0±2.4 n/×200 fields) compared to the CON group (16.6±2.7 n/×200 fields).The ability of EPCs to proliferate was reduced in the

  1. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    Science.gov (United States)

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  2. Perfusion Method for Intra-bone Marrow Collection and Stem Cell Transplantation: A Critical Review.

    Science.gov (United States)

    Korrapati, Narasimhulu; Nanganuru, Harikrishna Yadav

    2014-03-19

    A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside our bones. Bone marrow transplantation (BMT) is a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. In humans, bone marrow cells (BMCs) have usually been collected by multiple bone marrow aspirations from the iliac crest. We have established a new "perfusion" method for collecting BMCs with minimal contamination with the peripheral blood using the long bones of cynomolgus monkeys. This method has proven to be a simple and safe method for harvesting BMCs and reduces the risk of acute graft versus host disease in allogeneic BMT. Intra-bone marrow-BMT (IBM-BMT) provides distinct advantages because it recruits donor-derived hematopoietic stem cells and mesenchymal stem cells. IBM-BMT has been shown to currently be the best strategy for allogeneic BMT. Here we review the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) and show that this combination will become a powerful new clinical strategy for allogeneic BMT.

  3. Bone marrow and nonbone marrow Toll like receptor 4 regulate acute hepatic injury induced by endotoxemia.

    Directory of Open Access Journals (Sweden)

    Edith Hochhauser

    Full Text Available BACKGROUND: Toll-like receptors (TLRs are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4 is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS (septic shock model. METHODS: Wild type (WT, TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the liver or in the immune-hematopoietic system. Mice were injected with LPS and sacrificed 4 hours later. RESULTS: Compared to TLR4 deficient mice, WT mice challenged with LPS displayed increased serum liver enzymes and hepatic cellular inflammatory infiltrate together with increased serum and hepatic levels of interleukin 1β (IL-1β, tumor necrosis factor α (TNFα ,Up-regulation of hepatic mRNA encoding TLR4, IκB and c-jun expressions. TLR4 mutant mice transplanted with WT bone marrow were more protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS, as seen by IL-1β and TNFα levels. We then used hepatocytes (Huh7 and macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and 8000-fold respectively compared with the hepatocyte cell line. LPS administration induced TLR4 activation in a hepatocyte cell line in a dose dependent manner while TLR2 mRNA hardly changed. CONCLUSIONS: These results suggest that TLR4 activation of hepatocytes participate in the immediate response to LPS induced hepatic injury. However, in this response, the contribution of TLR4 on bone marrow derived cells is more significant than those of the hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing hepatic LPS induced injury.

  4. 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

    Energy Technology Data Exchange (ETDEWEB)

    Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [CEA, DSV, Serv Immunovirol, Inst Maladies Emergentes et Therapies Innovantes, Fontenay Aux Roses (France); Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [Univ Paris 11, UMR E01, Orsay (France); Negre, D.; Cosset, F. [Univ Lyon, UCB Lyon 1, IFR 128, F-69007 Lyon (France); Negre, D.; Cosset, F. [INSERM, U758, F-69007 Lyon (France); Negre, D.; Cosset, F.L. [Ecole NormaleSuper Lyon, F-69007 Lyon (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Lab Radiobiol, F-78352 Jouy En Josas (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Etude Genome, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Radiobiol Lab, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Etude Genome, F-78352 Jouy En Josas (France)

    2008-07-01

    Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myelo-ablative 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{sup +} bone marrow cells following gamma irradiation in cynomolgus macaques. 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 pseudo-typed 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 producing eGFP 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{sup +} 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. (authors)

  5. Tuberculosis in pediatric oncology and bone marrow transplantation patients.

    Science.gov (United States)

    Cruz, Andrea T; Airewele, Gladstone; Starke, Jeffrey R

    2014-08-01

    Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment, and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy.

  6. Mouse bone marrow cytogenetic damage produced by residues of tequila.

    Science.gov (United States)

    Madrigal-Bujaidar, E; Rojas, A; Ramos, A; Rosas, E; Díaz Barriga-Arceo, S

    1990-06-01

    Five concentrations (50-860 mg/kg) of residues obtained after distillation and lyophilization of commercial tequila were injected into mice for evaluation of chromosome aberrations, sister-chromatid exchanges, and proliferation kinetics in mouse bone marrow cells. Appropriate positive and negative controls were included. Our results showed significant dose-related increases of chromosomal aberrations starting at 50 mg/kg and for sister-chromatid exchanges at 430 mg/kg. Cellular proliferation kinetics showed no alterations. With these data we demonstrated that the residues of tequila are genotoxic in vivo.

  7. Contribution of bone marrow derived cells to pancreatic carcinogenesis

    Directory of Open Access Journals (Sweden)

    Christopher J Scarlett

    2013-03-01

    Full Text Available Pancreatic cancer is a complex, aggressive and heterogeneous malignancy driven by the multifaceted interactions within the tumor microenvironment. While it is known that the tumor microenvironment accommodates many cell types, each playing a key role in tumorigenesis, the major source of these stromal cells is not well understood. This review examines the contribution of bone marrow-derived cells (BMDC to pancreatic carcinogenesis, with respect to their role in constituting the tumor microenvironment. In particular, their role in supporting fibrosis, immunosuppression and neovascularisation will be discussed.

  8. Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia.

    Science.gov (United States)

    Sodani, Pietro; Isgrò, Antonella; Gaziev, Javid; Polchi, Paola; Paciaroni, Katia; Marziali, Marco; Simone, Maria Domenica; Roveda, Andrea; Montuoro, Aldo; Alfieri, Cecilia; De Angelis, Gioia; Gallucci, Cristiano; Erer, Buket; Isacchi, Giancarlo; Zinno, Francesco; Adorno, Gaspare; Lanti, Alessandro; Faulkner, Lawrence; Testi, Manuela; Andreani, Marco; Lucarelli, Guido

    2010-02-11

    Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day -59 to -11; 30 mg/m(2) fludarabine from day -17 to -11; 14 mg/kg busulfan starting on day -10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day -5 to -2. Fourteen patients received CD34(+)-mobilized peripheral blood and bone marrow progenitor cells; 8 patients received marrow graft-selected peripheral blood stem cells CD34(+) and bone marrow CD3/CD19-depleted cells. T-cell dose was adjusted to 2 x 10(5)/kg by fresh marrow cell addback at the time of transplantation. Both groups received cyclosporine for graft-versus-host disease prophylaxis for 2 months after transplantation. Two patients died (cerebral Epstein-Barr virus lymphoma or cytomegalovirus pneumonia), 6 patients reject their grafts, and 14 showed full chimerism with functioning grafts at a median follow-up of 40 months. None of the 14 patients who showed full chimerism developed acute or chronic graft-versus-host disease. These results suggest that maternal haploidentical hematopoietic stem cell transplantation is feasible in patients with thalassemia who lack a matched related donor.

  9. Effects of 200cH medications on mice bone marrow cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dorly de F. Buchi

    2011-07-01

    -culture. Bryonia alba increased Ly-6G, CD11c and CD11b expression ex vivo and when in co-culture CD11b was increased in adherent cells as well as decreased in nonadherent cells. With these results we have demonstrated that highly diluted medications act on immune cells activating macrophages, and changing the expression profile of hematopoietic lineage markers. Highly diluted medications are less toxic and cheaper than other commonly used medications and based on our observations, it is therefore conceivable that this medications which are able to act on bone marrow and immune cells may have a potential therapeutic use in clinical applications in diseases were the immune system is affected and also as regenerative medicine as it may allow proliferation and differentiation of progenitor cells.

  10. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.

    Science.gov (United States)

    Ribeiro, F V; Suaid, F F; Ruiz, K G S; Rodrigues, T L; Carvalho, M D; Nociti, F H; Sallum, E A; Casati, M Z

    2012-01-01

    This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (Pregeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.

  11. Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

    Science.gov (United States)

    Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

    2013-04-01

    Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

  12. Prevention of liver fibrosis by intrasplenic injection of high-density cultured bone marrow cells in a rat chronic liver injury model.

    Directory of Open Access Journals (Sweden)

    Jie Lian

    Full Text Available Endothelial progenitor cells (EPCs from bone marrow have proven to be functional for the prevention of liver fibrosis in chronic liver injury. However, expansion of EPCs in culture is complicated and expansive. Previously, we have established a simple method that could enrich and expand EPCs by simple seeding bone marrow cells in high density dots. The purpose of this study is to evaluate whether cells derived from high-density (HD culture of rat bone marrow cells could prevent the liver fibrosis in a chronic liver injury rat model, induced by carbon tetrachloride (CCl4. Flow cytometric analysis showed that cells from HD culture were enriched for EPCs, expressing high levels of EPC markers. Intrasplenic injection of HD cultured bone marrow cells in the CCl4-induced liver injury rat showed an enhanced antifibrogenic effect compared with animals treated with cells from regular-density culture. The antifibrogenic effect was demonstrated by biochemical and histological analysis 4 weeks post-transplantation. Furthermore, cells from HD culture likely worked through increasing neovascularization, stimulating liver cell proliferation, and suppressing pro-fibrogenic factor expression. HD culture, which is a simple and cost-effective procedure, could potentially be used to expand bone marrow cells for the treatment of liver fibrosis.

  13. Bone marrow mononuclear cells up-regulate toll-like receptor expression and produce inflammatory mediators in response to cigarette smoke extract.

    Directory of Open Access Journals (Sweden)

    Junmin Zhou

    Full Text Available Several reports link cigarette smoking with leukemia. However, the effects of cigarette smoke extract (CSE on bone marrow hematopoiesis remain unknown. The objective of this study was to elucidate the direct effects of cigarette smoke on human bone marrow hematopoiesis and characterize the inflammatory process known to result from cigarette smoking. Bone marrow mononuclear cells (BMCs from healthy individuals when exposed to CSE had significantly diminished CFU-E, BFU-E and CFU-GM. We found increased nuclear translocation of the NF-κB p65 subunit and, independently, enhanced activation of AKT and ERK1/2. Exposure of BMCs to CSE induced IL-8 and TGF-β1 production, which was dependent on NF-κB and ERK1/2, but not on AKT. CSE treatment had no effect on the release of TNF-α, IL-10, or VEGF. Finally, CSE also had a significant induction of TLR2, TLR3 and TLR4, out of which, the up-regulation of TLR2 and TLR3 was found to be dependent on ERK1/2 and NF-κB activation, but not AKT. These results indicate that CSE profoundly inhibits the growth of erythroid and granulocyte-macrophage progenitors in the bone marrow. Further, CSE modulates NF-κB- and ERK1/2-dependent responses, suggesting that cigarette smoking may impair bone marrow hematopoiesis in vivo as well as induce inflammation, two processes that proceed malignant transformation.

  14. Gene-modified bone marrow cell therapy for prostate cancer.

    Science.gov (United States)

    Wang, H; Thompson, T C

    2008-05-01

    There is a critical need to develop new and effective cancer therapies that target bone, the primary metastatic site for prostate cancer and other malignancies. Among the various therapeutic approaches being considered for this application, gene-modified cell-based therapies may have specific advantages. Gene-modified cell therapy uses gene transfer and cell-based technologies in a complementary fashion to chaperone appropriate gene expression cassettes to active sites of tumor growth. In this paper, we briefly review potential cell vehicles for this approach and discuss relevant gene therapy strategies for prostate cancer. We further discuss selected studies that led to the conceptual development and preclinical testing of IL-12 gene-modified bone marrow cell therapy for prostate cancer. Finally, we discuss future directions in the development of gene-modified cell therapy for metastatic prostate cancer, including the need to identify and test novel therapeutic genes such as GLIPR1.

  15. Effects of Sleep Deprivation on Mice Bone Marrow and Spleen B Lymphopoiesis.

    Science.gov (United States)

    Lungato, Lisandro; Nogueira-Pedro, Amanda; Carvalho Dias, Carolina; Paredes-Gamero, Edgar Julian; Tufik, Sergio; D'Almeida, Vânia

    2016-06-01

    B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response. Sleep is an essential event for the maintenance and integrity of all systems, including the immune system (IS). Thus, sleep deprivation (SD) causes problems in metabolism and homeostasis in many cell systems, including the IS. In this study, our goal was to determine changes in B lymphocytes from the bone marrow (BM) and spleen after SD. Three-month-old male Swiss mice were used. These mice were sleep deprived through the modified multiple platform method for different periods (24, 48, and 72 h), whereas another group was allowed to sleep for 24 h after 72 h of SD (rebound group) and a third group was allowed to sleep normally during the entire experiment. After this, the spleen and BM were collected, and cell analyses were performed. The numbers of B lymphocytes in the BM and spleen were reduced by SD. Additionally, reductions in the percentage of lymphocyte progenitors and their ability to form colonies were observed. Moreover, an increase in the death of B lymphocytes from the BM and spleen was associated with an increase in oxidative stress indicators, such as DCFH-DA, CAT, and mitochondrial SOD. Rebound was not able to reverse most of the alterations elicited by SD. The reduction in B lymphocytes and their progenitors by cell death, with a concomitant increase in oxidative stress, showed that SD promoted a failure in B lymphopoiesis.

  16. An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites

    Directory of Open Access Journals (Sweden)

    Mónica S. Ventura Ferreira

    2016-01-01

    Full Text Available Abstract Background Bone marrow (BM niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D geometry. Methods Here, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs and hematopoietic stem and progenitor cells (HSPCs. Structural components included 3D β-tricalcium phosphate (β-TCP scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM. Results In vitro, β-TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation. Conclusions Our tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease.

  17. Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.

    Directory of Open Access Journals (Sweden)

    Kentaro Yoshioka

    Full Text Available Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC, leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice.

  18. Treatment of Moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells.

    Science.gov (United States)

    Wu, R; Su, N; Zhang, Z; Jia, F

    2015-07-06

    This study discusses the clinical efficacy of multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and use of simvastatin in the treatment of moyamoya disease. Seventy-eight patients [control group (group A), 39 patients; experimental group (group B), 39 patients] with moyamoya disease were selected. Group A underwent indirect revascularization, and group B, in addition to indirect revascularization, received alternate subcutaneous injections from day 7 post-surgery. The number and differentiation of the mobilized bone marrow stem cells were detected by the proportion of hematopoietic progenitor cell (HPCs) in mononuclear cells (MNCs) in the peripheral blood. There was no statistical difference in the BI (80.2 ± 13.7) and NIHSS (6.7 ± 2.3) scores between the groups before treatment (P > 0.05). The CSS score of group B was 13.5 ± 0.6 and there was a statistical significance compared to group A (18.2 ± 0.8) (P 0.05) and the proportions of CD34+ CDl33+ cells in MNCs in peripheral blood in groups A and B at 30 days after surgery were significantly higher than those before surgery (P moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and simvastatin is a safe and effective method as it can promote recovery of neurological functions and improve patients' daily living abilities and quality of life.

  19. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    Science.gov (United States)

    Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

    2013-01-01

    The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

  20. Development of bone marrow mesenchymal stem cell culture in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; PENG Li-pan; WU Nan; LI Le-ping

    2012-01-01

    Objective To review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).Data sources The data cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms were “bone marrow mesenchymal stem cell" and "cell culture".Study selection Articles regarding the in vitro development of BM-MSCs culture,as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs.3D.Results Improving the culture conditions increases the proliferation and reduces the differentiation.Optimal values for many culture parameters remain to be identified.Expansion of BM-MSCs under defined conditions remains challenging,including the development of optimal culture conditions for BMSC and large-volume production systems.Conclusions Expansion of BM-MSCs under defined conditions remains challenges,including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems.Optimal values for many culture parameters remain to be identified.

  1. New approaches to graft engineering for haploidentical bone marrow transplantation.

    Science.gov (United States)

    Handgretinger, Rupert

    2012-12-01

    Haploidentical transplantation opens the possibility to offer this treatment to a large number of patients with an otherwise incurable disease, such as some hematologic or oncologic malignancies, inborn or acquired bone marrow failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Initial attempts at haploidentical transplantation using unmanipulated bone marrow were associated with a high transplant-related mortality. However, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes compared to previous decades. Methods for the in vitro depletion of T lymphocytes from mobilized peripheral blood stem cells (PBSC) to prevent graft-versus-host disease (GvHD) have facilitated the wider use and acceptance of haploidentical transplantation in children and adult patients. Besides in vitro T-cell depletion techniques, other methods, such as the isolation of alloreactive natural killer (NK) cells, virus-specific T lymphocytes, and other effector or regulatory cells are nowadays available to rapidly rebuild the immune system after haploidentical transplantation for the prevention of severe infections or relapses of the underlying diseases.

  2. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration.

    Science.gov (United States)

    Berumen-Nafarrate, Edmundo; Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

    2013-01-01

    The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis.

  3. Degradation of polysaccharide hydrogels seeded with bone marrow stromal cells.

    Science.gov (United States)

    Jahromi, Shiva H; Grover, Liam M; Paxton, Jennifer Z; Smith, Alan M

    2011-10-01

    In order to produce hydrogel cell culture substrates that are fit for the purpose, it is important that the mechanical properties are well understood not only at the point of cell seeding but throughout the culture period. In this study the change in the mechanical properties of three biopolymer hydrogels alginate, low methoxy pectin and gellan gum have been assessed in cell culture conditions. Samples of the gels were prepared encapsulating rat bone marrow stromal cells which were then cultured in osteogenic media. Acellular samples were also prepared and incubated in standard cell culture media. The rheological properties of the gels were measured over a culture period of 28 days and it was found that the gels degraded at very different rates. The degradation occurred most rapidly in the order alginate > Low methoxy pectin > gellan gum. The ability of each hydrogel to support differentiation of bone marrow stromal cells to osteoblasts was also verified by evidence of mineral deposits in all three of the materials. These results highlight that the mechanical properties of biopolymer hydrogels can vary greatly during in vitro culture, and provide the potential of selecting hydrogel cell culture substrates with mechanical properties that are tissue specific.

  4. Bone Marrow Gene Therapy for HIV/AIDS.

    Science.gov (United States)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-17

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  5. The effects of simulated hypogravity on murine bone marrow cells

    Science.gov (United States)

    Lawless, Desales

    1989-01-01

    Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

  6. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    Directory of Open Access Journals (Sweden)

    Edmundo Berumen-Nafarrate

    2013-01-01

    Full Text Available The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis.

  7. Entonox as a sedative for bone marrow aspiration and biopsy.

    Science.gov (United States)

    Gudgin, E J; Besser, M W; Craig, J I O

    2008-02-01

    Bone marrow aspiration and biopsy can be a painful procedure. Sedation techniques may make this investigation more acceptable to patients, but have the potential to cause life-threatening complications, as well as requiring additional staff and equipment for safe administration. We assessed the use of Entonox, a 50 : 50 mix of nitrous oxide and oxygen, as a sedation and analgesic agent, and compared it to previous experience with the intravenous (i.v.) benzodiazepine midazolam. Patients' perception of pain, and both the operator and patient's views on the ease of the procedure and safety factors were recorded. Twenty-two patients who had previously required i.v. midazolam sedation (16), or who requested sedation (6) were studied. Fifteen of 16 (94%) found Entonox better or equal to midazolam, and only one patient (6%) found it worse. There were no serious adverse events due to Entonox. We have shown, in this small group of patients, that Entonox is an effective, safe alternative to intravenous midazolam for sedation during bone marrow biopsy, and is considered acceptable by both patients and staff. It has the major advantage that no additional staff or facilities are required for safe administration or monitoring the patient during or after the procedure.

  8. Ex vivo expansion of Primate CD34+ Cells isolated from Bone Marrow and Human Bone Marrow Mononuclear Cells using a Novel Scaffold

    Directory of Open Access Journals (Sweden)

    Devaprasad D

    2009-01-01

    Full Text Available Bone marrow derived CD34+ cells have been in clinical application in patients with haematological malignancies. One of the major problems with this treatment is the non-availability of matched donors or the necessity of multiple transfusions depending upon the pathology. Recently evidences have been accumulating to prove the safety and efficacy of autologous CD34+ cells in diseases such as myocardial dysfunction, peripheral vascular diseases and neurological certain conditions. However there are only a few reports in the literature on ex vivo expansion of the bone marrow derived CD34+ cells. We have in two different studies proven that isolated CD34+ cells from baboon bone marrow and non-isolated BMMNCs from human bone marrow could be expanded with increase in percentage of CD34+ cells using a novel scaffold.

  9. Electrostimulation and morphologic study of the nerves to the bone marrow of the albino rat.

    Science.gov (United States)

    DePace, D M; Webber, R H

    1975-01-01

    The innervation of the bone marrow of the albino rat was investigated by electrostimulation and morphological methods. Stimulation of the lumbar sympathetic trunks resulted in the release of reticulocytes and neutrophils into the circulating blood. The effects of stimulation on other cell types in the bone marrow could not be definitely established. It was concluded that the nerve fibers to the bone marrow were distributed to the arteries. It is postulated that the transmitter substance released at the autonomic nerve endings may have an effect upon the permeability of the venous sinusiods and the mobility of the blood cells in the marrow parenchyma resulting in their release into the circulating blood.

  10. 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...... and capillarization, with the development of continuous sheets of basement membrane material beneath endothelial cells....

  11. 2012478 Biological characteristics of bone marrow mesenchymal stem cells and JAK2 mutation in myeloproliferative neoplasms

    Institute of Scientific and Technical Information of China (English)

    田竑

    2012-01-01

    Objective To study the biological characteristics of bone marrow mesenchymal stem cells(BMSCs) and detect JAK2 mutation in BMSCs from myeloproliferative neoplasms(MPN) patients. Methods JAK2 V617F mutation and exon 12 mutation in 70 MPN patients’ blood or bone marrow samples were detected.

  12. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    NARCIS (Netherlands)

    S. James (Sally); J. Fox (James); F. Afsari (Farinaz); J. Lee (Jennifer); S. Clough (Sally); C. Knight (Charlotte); J. Ashmore (James); P. Ashton (Peter); O. Preham (Olivier); M.J. Hoogduijn (Martin); R.D.A.R. Ponzoni (Raquel De Almeida Rocha); Y. Hancock; M. Coles (Mark); P.G. Genever (Paul)

    2015-01-01

    textabstractBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis

  13. Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

    Science.gov (United States)

    Sikora, Agnieszka; Wiorkowski, Krzysztof; Szara, Paulina; Drabko, Katarzyna

    2014-01-01

    Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students.

  14. B cell-autonomous somatic mutation deficit following bone marrow transplant

    NARCIS (Netherlands)

    Glas, A.M.

    2000-01-01

    The bone marrow is the major haematopoietic organ and is critically involved in the production of all formed blood elements in postnatal life. The bone marrow contains rapidly dividing cells and therefore is sensitive to DNA damaging agents. In certain types of cancers where a high dose of radiation

  15. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.

    Science.gov (United States)

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically "fatless" mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation.

  16. IMPACT OF IMMUNOGENETIC POLYMORPHISMS ON IMMUNE RESPONSE AND CLINICAL FEATURES IN BONE MARROW FAILURE SYNDROMES

    OpenAIRE

    2008-01-01

    Hematopietic stem cells (HSC) are responsible for the production of mature blood cells in bone marrow; peripheral pancytopenia may result from several different conditions, including hematological or extra-hematological diseases (mostly cancers) affecting the marrow function as well as primary failure of hematopoiesis. Although the clinical presentation may appear homogeneous, primary bone marrow failure syndromes are a heterogeneous group of diseases with specific pathogenic mechanisms, whic...

  17. New experimental approach to treatment of radiation-induced bone marrow aplasia: ex vivo expansion of hematopoietic cells; Nouvelle approche experimentale du traitement de l`aplasie medullaire radio-induite

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

    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).

  18. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  19. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  20. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  1. High-fidelity organic preservation of bone marrow in ca. 10 Ma amphibians

    Science.gov (United States)

    McNamara, Maria E.; Orr, Patrick J.; Kearns, Stuart L.; Alcalá, Luis; Anadón, Pere; Peñalver-Mollá, Enrique

    2006-08-01

    Bone marrow in ca. 10 Ma frogs and salamanders from the Miocene of Libros, Spain, represents the first fossilized example of this extremely decay-prone tissue. The bone marrow, preserved in three dimensions as an organic residue, retains the original texture and red and yellow color of hematopoietic and fatty marrow, respectively; moldic osteoclasts and vascular structures are also present. We attribute exceptional preservation of the fossilized bone marrow to cryptic preservation: the bones of the amphibians formed protective microenvironments, and inhibited microbial infiltration. Specimens in which bone marrow is preserved vary in their completeness and articulation and in the extent to which the body outline is preserved as a thin film of organically preserved bacteria. Cryptic preservation of these labile tissues is thus to a large extent independent of, and cannot be predicted by, the taphonomic history of the remainder of the specimen.

  2. A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

    Science.gov (United States)

    Takatori, T; Tomii, S; Terazawa, K; Nagao, M; Kanamori, M; Tomaru, Y

    1991-01-01

    The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

  3. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2015-01-01

    Full Text Available In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  4. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffoldin vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi-tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial ifbrillary acidic protein and a low level of expression of neuron-spe-ciifc enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These ifndings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi-tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  5. The effects of bone marrow aspirate, bone graft, and collagen composites on fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Sandri, Monica

    2012-01-01

    contamination, and non union as well as the potential risk of disease transmission. Hydroxyapatite and collagen composites (HA/Collagen) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effects of newly developed HA/Collagen-composites with and without bone...... marrow aspirate (BMA) on enhancement of bone implant fixation. Method: Titanium alloy implants were inserted into bilateral femoral condyles of eight skeletally mature sheep, four implants per sheep. The implant had a circumferential gap of 2 mm. The gap was filled with: HA/Collagen; HA/Collagen...... and histomorphometry between autograft and allograft groups. The implants in both the HA/Collagen and HA/Collagen-BMA groups were mostly surrounded by fibrous tissue. Thus, mechanical testing of these samples was impossible. The histomorphometry results showed significantly more new bone and bone ongrowth...

  6. Allogenous bone grafts improved by bone marrow stem cells and platelet growth factors: clinical case reports.

    Science.gov (United States)

    Filho Cerruti, Humberto; Kerkis, Irina; Kerkis, Alexandre; Tatsui, Nelson Hidekazu; da Costa Neves, Adriana; Bueno, Daniela Franco; da Silva, Marcelo Cavenaghi Pereira

    2007-04-01

    In order to increase the amount of available bone where dental implants must be placed, the present study has associated platelet-rich plasma (PRP) and mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32 patients aged between 45 and 75 years old. The MNC attainment and the adherence to the BS were confirmed through histology, cell culture, and scanning electron microscopy. The clinical results, analyzed by computed tomography, have showed that the scaffolds were well integrated and adapted to the cortical bone. We can conclude that the process of healing observed in the patients was due to the presence of mesenchymal stem cell in MNC fraction in the bone grafts.

  7. Bone marrow segmentation based on a combined consideration of transverse relaxation processes and Dixon oscillations.

    Science.gov (United States)

    Balasubramanian, Mukund; Jarrett, Delma Y; Mulkern, Robert V

    2016-05-01

    The aim of this study was to demonstrate that gradient-echo sampling of single spin echoes can be used to isolate the signal from trabecular bone marrow, with high-quality segmentation and surface reconstructions resulting from the application of simple post-processing strategies. Theoretical expressions of the time-domain single-spin-echo signal were used to simulate signals from bone marrow, non-bone fatty deposits and muscle. These simulations were compared with and used to interpret signals obtained by the application of the gradient-echo sampling of a spin-echo sequence to image the knee and surrounding tissues at 1.5 T. Trabecular bone marrow has a much higher reversible transverse relaxation rate than surrounding non-bone fatty deposits and other musculoskeletal tissues. This observation, combined with a choice of gradient-echo spacing that accentuates Dixon-type oscillations from chemical-shift interference effects, enabled the isolation of bone marrow signal from surrounding tissues through the use of simple image subtraction and thresholding. Three-dimensional renderings of the marrow surface were then readily generated with this approach - renderings that may prove useful for bone morphology assessment, e.g. for the measurement of femoral anteversion. In conclusion, understanding the behavior of signals from bone marrow and surrounding tissue as a function of time through a spin echo facilitates the segmentation and reconstruction of bone marrow surfaces using straightforward post-processing strategies that are typically available on modern radiology workstations.

  8. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  9. Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice

    Science.gov (United States)

    Koh, Young Jun; Kang, Shinae; Lee, Hyuek Jong; Choi, Tae-Saeng; Lee, Ho Sub; Cho, Chung-Hyun; Koh, Gou Young

    2007-01-01

    Little is known about whether bone marrow–derived circulating progenitor cells (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a role in expanding adipocyte number during adipose tissue growth. Using a mouse bone marrow transplantation model, we addressed whether BMDCPCs can transdifferentiate into adipocytes under standard conditions as well as in the settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF. We also addressed the possibility of transdifferentiation to adipocytes in a murine parabiosis model. In each of these settings, our findings indicated that BMDCPCs did not transdifferentiate into either unilocular or multilocular adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic macrophages in adipose tissues — which resembled transdifferentiated multilocular adipocytes by appearance, but displayed cell surface markers characteristic for macrophages — in the absence of adipocyte marker expression. When exposed to adipogenic medium in vitro, bone marrow cells differentiated into multilocular, but not unilocular, adipocytes, but transdifferentiation was not observed in vivo, even in the contexts of adipose tissue regrowth or dermal wound healing. Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in vivo and play little, if any, role in expanding the number of adipocytes during the growth of adipose tissues. PMID:18060029

  10. Strain energy density gradients in bone marrow predict osteoblast and osteoclast activity: a finite element study.

    Science.gov (United States)

    Webster, Duncan; Schulte, Friederike A; Lambers, Floor M; Kuhn, Gisela; Müller, Ralph

    2015-03-18

    Huiskes et al. hypothesized that mechanical strains sensed by osteocytes residing in trabecular bone dictate the magnitude of load-induced bone formation. More recently, the mechanical environment in bone marrow has also been implicated in bone׳s response to mechanical stimulation. In this study, we hypothesize that trabecular load-induced bone formation can be predicted by mechanical signals derived from an integrative µFE model, incorporating a description of both the bone and marrow phase. Using the mouse tail loading model in combination with in vivo micro-computed tomography (µCT) we tracked load induced changes in the sixth caudal vertebrae of C57BL/6 mice to quantify the amount of newly mineralized and eroded bone volumes. To identify the mechanical signals responsible for adaptation, local morphometric changes were compared to micro-finite element (µFE) models of vertebrae prior to loading. The mechanical parameters calculated were strain energy density (SED) on trabeculae at bone forming and resorbing surfaces, SED in the marrow at the boundary between bone forming and resorbing surfaces, along with SED in the trabecular bone and marrow volumes. The gradients of each parameter were also calculated. Simple regression analysis showed mean SED gradients in the trabecular bone matrix to significantly correlate with newly mineralized and eroded bone volumes R(2)=0.57 and 0.41, respectively, pbone marrow plays a significant role in determining osteoblast and osteoclast activity.

  11. Comparisons of Mouse Mesenchymal Stem Cells in Primary Adherent Culture of Compact Bone Fragments and Whole Bone Marrow

    Directory of Open Access Journals (Sweden)

    Yiting Cai

    2015-01-01

    Full Text Available The purification of mouse bone marrow mesenchymal stem cells (BMSCs by using the standard method of whole bone marrow adherence to plastic still remains ineffective. An increasing number of studies have indicated compact bone as an alternative source of BMSCs. We isolated BMSCs from cultured compact bone fragments and investigated the proliferative capacity, surface immunophenotypes, and osteogenic and adipogenic differentiations of the cells after the first trypsinization. The fragment culture was based on the fact that BMSCs were assembled in compact bones. Thus, the procedure included flushing bone marrow out of bone cavity and culturing the fragments without any collagenase digestion. The cell yield from cultured fragments was slightly less than that from cultured bone marrow using the same bone quantity. However, the trypsinized cells from cultured fragments exhibited significantly higher proliferation and were accompanied with more CD90 and CD44 expressions and less CD45 expression. The osteogenic and adipogenic differentiation capacity of cells from cultured fragments were better than those of cells from bone marrow. The directly adherent culture of compact bone is suitable for mouse BMSC isolation, and more BMSCs with potentially improved proliferation capacity can be obtained in the primary culture.

  12. File list: NoD.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.50.AllAg.Leukemic_bone_marrow mm9 No description Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  13. File list: InP.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Leukemic_bone_marrow mm9 Input control Blood Leukemic bone marrow ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  14. File list: NoD.Bld.20.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.20.AllAg.Leukemic_bone_marrow mm9 No description Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.20.AllAg.Leukemic_bone_marrow.bed ...

  15. File list: NoD.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.05.AllAg.Leukemic_bone_marrow mm9 No description Blood Leukemic bone marrow... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  16. File list: NoD.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.10.AllAg.Bone_Marrow_Cells hg19 No description Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  17. File list: InP.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Bone_Marrow_Cells hg19 Input control Blood Bone Marrow Cells http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  18. File list: InP.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Bone_Marrow_Cells hg19 Input control Blood Bone Marrow Cells http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  19. File list: InP.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Bone_Marrow_Cells mm9 Input control Blood Bone Marrow Cells ERX534...209471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  20. File list: NoD.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.50.AllAg.Bone_Marrow_Cells hg19 No description Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  1. File list: NoD.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.20.AllAg.Bone_Marrow_Cells hg19 No description Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  2. File list: InP.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Bone_Marrow_Cells mm9 Input control Blood Bone Marrow Cells ERX534...036746 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  3. File list: InP.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Bone_Marrow_Cells hg19 Input control Blood Bone Marrow Cells http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  4. File list: InP.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Bone_Marrow_Cells mm9 Input control Blood Bone Marrow Cells ERX534...036746 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  5. File list: NoD.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.05.AllAg.Bone_Marrow_Cells mm9 No description Blood Bone Marrow Cells DRX03...833680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  6. File list: NoD.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.50.AllAg.Bone_Marrow_Cells mm9 No description Blood Bone Marrow Cells SRX83...833545 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  7. File list: InP.Bld.50.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Bone_Marrow_Cells mm9 Input control Blood Bone Marrow Cells ERX534...209471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Bone_Marrow_Cells.bed ...

  8. File list: NoD.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.20.AllAg.Bone_Marrow_Cells mm9 No description Blood Bone Marrow Cells DRX03...833545 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  9. File list: NoD.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.10.AllAg.Bone_Marrow_Cells mm9 No description Blood Bone Marrow Cells DRX03...833680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.10.AllAg.Bone_Marrow_Cells.bed ...

  10. File list: InP.Bld.20.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Bone_Marrow_Cells hg19 Input control Blood Bone Marrow Cells http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.20.AllAg.Bone_Marrow_Cells.bed ...

  11. File list: NoD.Bld.05.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.05.AllAg.Bone_Marrow_Cells hg19 No description Blood Bone Marrow Cells http...://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.05.AllAg.Bone_Marrow_Cells.bed ...

  12. File list: InP.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Leukemic_bone_marrow mm9 Input control Blood Leukemic bone marrow ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Leukemic_bone_marrow.bed ...

  13. File list: InP.Bld.10.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Leukemic_bone_marrow mm9 Input control Blood Leukemic bone marrow ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.Leukemic_bone_marrow.bed ...

  14. File list: InP.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Leukemic_bone_marrow mm9 Input control Blood Leukemic bone marrow ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Leukemic_bone_marrow.bed ...

  15. Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment.

    Directory of Open Access Journals (Sweden)

    Maria Rostovskaya

    Full Text Available Bone marrow mesenchymal stromal cells (BM MSCs represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.

  16. Isolation of Murine Bone Marrow Derived Mesenchymal Stem Cells using Twist2 Cre Transgenic Mice

    Science.gov (United States)

    Liu, Yaling; Wang, Liping; Fatahi, Reza; Kronenberg, Mark; Kalajzic, Ivo; Rowe, David; Li, Yingcui; Maye, Peter

    2010-01-01

    While human bone marrow derived mesenchymal stem cells (BMSCs) are of great interest for their potential therapeutic value, its murine equivalent remains an important basic research model that can provide critical insights into the biology of this progenitor cell population. Here we present a novel transgenic strategy that allowed for the selective identification and isolation of murine BMSCs at the early stages of stromal cell culture. This strategy involved crossing Twist2 –Cre mice with Cre reporter mice such as Z/EG or Ai9, which express EGFP or Tomato fluorescent protein, respectively, upon Cre mediated excision of a stop sequence. Using this approach, we identified an adherent fluorescent protein+ cell population (T2C+) that is present during the earliest stages of colony formation and by day 5 of culture represents ~20% of the total cell population. Cell surface profiling by flow cytometry showed that T2C+ cells are highly positive for SCA1 and CD29 and negative for CD45, CD117, TIE2, and TER119. Isolation of T2C+ cells by FACS selected for a cell population with skeletal potential that can be directed to differentiate into osteoblasts, adipocytes, or chondrocytes. We also demonstrated in a calvarial bone defect model that T2C+ cells retain a strong efficacy for osteogenic repair and can support a hematopoietic environment. Collectively, these studies provide evidence that the Twist2-Cre x Cre reporter breeding strategy can be used to positively identify and isolate multipotent murine BMSCs. PMID:20673822

  17. Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Zhenjiu Zhu

    Full Text Available Prostaglandin E2 (PGE2 has been reported to modulate angiogenesis, the process of new blood vessel formation, by promoting proliferation, migration and tube formation of endothelial cells. Endothelial progenitor cells are known as a subset of circulating bone marrow mononuclear cells that have the capacity to differentiate into endothelial cells. However, the mechanism underlying the stimulatory effects of PGE2 and its specific receptors on bone marrow-derived cells (BMCs in angiogenesis has not been fully characterized. Treatment with PGE2 significantly increased the differentiation and migration of BMCs. Also, the markers of differentiation to endothelial cells, CD31 and von Willebrand factor, and the genes associated with migration, matrix metalloproteinases 2 and 9, were significantly upregulated. This upregulation was abolished by dominant-negative AMP-activated protein kinase (AMPK and AMPK inhibitor but not protein kinase, a inhibitor. As a functional consequence of differentiation and migration, the tube formation of BMCs was reinforced. Along with altered BMCs functions, phosphorylation and activation of AMPK and endothelial nitric oxide synthase, the target of activated AMPK, were both increased which could be blocked by EP4 blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3. The pro-angiogenic role of PGE2 could be repressed by EP4 blocking peptide and retarded in EP4(+/- mice. Therefore, by promoting the differentiation and migration of BMCs, PGE2 reinforced their neovascularization by binding to the receptor of EP4 in an AMPK-dependent manner. PGE2 may have clinical value in ischemic heart disease.

  18. Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial

    Science.gov (United States)

    Taylor, Doris A.; Perin, Emerson C.; Willerson, James T.; Zierold, Claudia; Resende, Micheline; Carlson, Marjorie; Nestor, Belinda; Wise, Elizabeth; Orozco, Aaron; Pepine, Carl J.; Henry, Timothy D.; Ellis, Stephen G.; Zhao, David X. M.; Traverse, Jay H.; Cooke, John P.; Schutt, Robert C.; Bhatnagar, Aruni; Grant, Maria B.; Lai, Dejian; Johnstone, Brian H.; Sayre, Shelly L.; Moyé, Lem; Ebert, Ray F.; Bolli, Roberto; Simari, Robert D.; Cogle, Christopher R.

    2016-01-01

    In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4+ BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy—even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials. PMID:26590374

  19. Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model.

    Science.gov (United States)

    Luangphakdy, V; Shinohara, K; Pan, H; Boehm, C; Samaranska, A; Muschler, G F

    2015-01-12

    Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP-2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 %±1.2 and 11.2 %±1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

  20. Protecting the interests of the child bone marrow donor.

    Science.gov (United States)

    Terry, Louise M; Campbell, Anne

    2004-01-01

    At a time when designer babies have been created to act as cord blood donors to sick siblings, ethical debate has focused predominantly on the extent to which it is acceptable to create one human being to assist another. However, children are frequently used this way, by their families and doctors who extract their bone marrow, to try to save the life of another, usually a sibling. With any life-threatening illness, there is the possibility that the urgency of the sick sibling's need means that the short-term welfare of the donor child receives less attention than it should by parents and doctors. This article suggests ways to protect the interests of such children and empower them within the decision-making process and concludes that the drive to save life must be tempered by recognition of the intrinsic worth of donor children and their rights not to be exploited.

  1. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  2. Bone marrow processing on the Haemonetics V50 cell separator.

    Science.gov (United States)

    Anderson, N A; Cornish, J M; Godwin, V; Gunstone, M J; Oakhill, A; Pamphilon, D H

    1990-01-01

    We have processed 27 bone marrow (BM) harvests using the Haemonetics V50 cell separator with a paediatric plasmapheresis set and programmed for lymphocyte collection. The mean starting volume of 843 mL was processed in 6-8 cycles to a buffy coat (BC) with a mean volume of 230 mL. The mean starting mononuclear cell (MNC) count was 1.22 x 10 8/kg recipient weight, and recovery was 92%. Clonogenic potential of the BC was assessed using CFU-GM assays and recovery was measured after cryopreservation or purging. On 4 occasions where major ABO incompatibility existed between donor and recipient, both BM and BC were consecutively diluted in compatible blood and processed twice. This achieved a calculated reduction in donor erythrocytes of 98%. The procedure was efficient and yielded a BC fraction suitable for cryopreservation and purging. Adequate stem-cells were retained as verified by CFU-GM assays and documentation of stable engraftment.

  3. MRI of intracranial toxoplasmosis after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, U.; Doerfler, A.; Forsting, M. [Department of Neuroradiology, University Hospital, Essen (Germany); Maschke, M. [Department of Neurology, University Hospital Essen (Germany); Prumbaum, M. [Department of Bone Marrow Transplantation, University Hospital Essen (Germany)

    2000-01-01

    Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent. (orig.)

  4. Assessment of bone marrow inflammation in patients with myelofibrosis: an {sup 18}F-fluorodeoxyglucose PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Alchalby, Haefaa; Triviai, Ioanna; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany); Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany)

    2015-04-01

    Myelofibrosis is a haematopoietic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary haematopoiesis. The aim of this study was to determine if {sup 18}F-FDG PET/CT can be used to noninvasively visualize and quantify the extent and activity of bone marrow involvement. In 30 patients, the biodistribution of {sup 18}F-FDG was analysed by measuring the standardized uptake value in the bone marrow compartment and spleen. Imaging findings were compared with laboratory, cytogenetic and histopathological data. Retention of {sup 18}F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, ranging from mildly increased uptake in the central skeleton to extensive uptake in most parts of the skeleton. The extent of bone marrow involvement decreased over time from initial diagnosis (r{sub s} = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (r{sub s} = -0.37, p = 0.04). There was a significant positive correlation between the metabolic activity of the bone marrow and that of the spleen (p = 0.04). {sup 18}F-FDG PET/CT is as a promising technique for the quantitation of bone marrow inflammation in myelofibrosis. Our data indicate that the intensity of bone marrow {sup 18}F-FDG uptake decreases as bone marrow fibrosis increases. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET. (orig.)

  5. In vivo lipid diffusion coefficient measurements in rat bone marrow.

    Science.gov (United States)

    Ababneh, Zaid Q; Beloeil, Helene; Berde, Charles B; Ababneh, Anas M; Maier, Stephan E; Mulkern, Robert V

    2009-07-01

    The diffusion coefficient of lipids, D(l), within bone marrow, fat deposits and metabolically active intracellular lipids in vivo will depend on several factors including the precise chemical composition of the lipid distribution (chain lengths, degree of unsaturation, etc.) as well as the temperature. As such, D(l) may ultimately prove of value in assessing abnormal fatty acid distributions linked to diseases such as cystic fibrosis, diabetes and coronary heart disease. A sensitive temperature dependence of D(l) may also prove of value for MR-guided thermal therapies for bone tumors or disease within other fatty tissues like the breast. Measuring diffusion coefficients of high molecular weight lipids in vivo is, however, technically difficult for a number of reasons. For instance, due to the much lower diffusion coefficients compared to water, much higher b factors than those used for central nervous system applications are needed. In addition, the pulse sequence design must incorporate, as much as possible, immunity to motion, susceptibility and chemical shift effects present whenever body imaging is performed. In this work, high b-factor line scan diffusion imaging sequences were designed, implemented and tested for D(l) measurement using a 4.7-T horizontal bore animal scanner. The gradient set available allowed for b factors as high as 0.03 micros/nm(2) (30,000 s/mm(2)) at echo times as short as 42 ms. The methods were used to measure lipid diffusion coefficients within the marrow of rat paws in vivo, yielding lipid diffusion coefficients approximately two orders of magnitude smaller than typical tissue water diffusion coefficients. Phantom experiments that demonstrate the sensitivity of lipid diffusion coefficients to chain length and temperature were also performed.

  6. Vancomycin Utilization Review in Patients Undergoing Bone MarrowTransplantation

    Directory of Open Access Journals (Sweden)

    Saghar Taheri

    2015-10-01

    Full Text Available Background:  Infections  in  neutropenic  patients  are  considered  as  major  causes  of  mortality and the emergence of drug resistance. Gram positive bacterial infections are crucially important to be covered if indicated. Vancomycin is active against most Gram positive bacteria including Methicillin Resistant Staphylococcus Aureus (MRSA. In this study, we evaluated the appropriate utilization of this agent in bone marrow transplantation (BMT patients.Methods: In a cross sectional study, all patients who received vancomycin in a seven months period at bone marrow transplantation research center in Shariati teaching hospital in Tehran, Iran, were entered to the study. Clinical and preclinical parameters such as serum creatinine, microbial culture, antibacterial sensitivity, WBC count and fever were collected and recorded for analysis. We also measured vancomycin trough level after administration of three doses.Results: Fifty one patients were entered in the study and reviewed in two adult BMT wards. The age range was 18 to 65 years. Most patients received allogenic versus autologous transplantation (56.9%, 43.1%. About 80% of the vancomycin used for the patients with febrile neutropenia was compatible with National Comprehensive Cancer Network (NCCN guideline. 21.6% of patients received appropriate doses. Vancomycin trough serum concentration range was 15.0±11.9 μg/mL.Conclusion: Vancomycin is an antibiotic used to treat resistant gram-positive infections and must be prescribed by a specialist. Vancomycin wrong dosing or initiation prescribing with dose 1 gr/q12h increases the resistance and toxicity to drug, and cause an inappropriate response to the drug.

  7. Histologia da medula óssea Bone marrow histology

    Directory of Open Access Journals (Sweden)

    Antonio C. Alves

    2009-01-01

    Full Text Available A biópsia de medula óssea, após a utilização da agulha de Jamshidi, tornou- se um evento de rotina em virtude da simplificação na obtenção do material. A adequação das dimensões da amostra e a diminuição do tempo de descalcificação melhoraram muito a qualidade histológica e possibilitaram ao patologista um aprofundamento da interpretação morfológica das doenças hematológicas e não hematológicas. Para um laudo correto é necessário o conhecimento do tecido hematopoético normal, suas diferentes linhagens celulares, variações dependentes da idade e integração com outros dados clínicos e laboratoriais.The bone marrow biopsy after the introduction of the Jamshidi needle has come into a routine practice due to the facilitation to obtain good sample. Due to the adequate size of the sample, the decalcification time decreased and consequently the histological quality improved allowing to the pathologist a more deep and precise morphological interpretation and diagnosis of the hematological and non- hematological disorders. For a correct diagnosis, the pathologist should be acquainted with the normal histology of the bone marrow parenchyma, it variations depending on age, as well as with the clinico- laboratorial data to integrate them with the morphological features.

  8. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

    NARCIS (Netherlands)

    Song, G.; Habibovic, P.; Bao, C.; Hu, J.; Blitterswijk, van C.A.; Yuan, H.; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagl

  9. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    Directory of Open Access Journals (Sweden)

    Verônica Fernandes Vianna

    2013-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  10. Quantitative and qualitative assessment of reactive hematopoietic bone marrow in aplastic anemia using MR spectroscopy with variable echo times

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Kumazaki, Tatsuo [Department of Radiology, Nippon Medical School, Tokyo (Japan)

    2002-01-01

    Objective: To assess quantitative and qualitative differences in water components between normal bone marrow and reactive hematopoietic marrow in aplastic anemia using magnetic resonance (MR) spectroscopy with variable echo times (TEs). Design: Water content, T2 value of the water component, and signal change in water related to TE were assessed in normal bone marrow and reactive hematopoietic bone marrow by a stimulated echo acquisition mode with TEs of 30, 45, 60, and 90 ms. Patients: Six patients with aplastic anemia (13-84 years) and seven normal volunteers (25-38 years) were examined. Results and conclusion: Reactive hematopoietic marrow showed significantly higher water content than normal bone marrow. The T2 value of water components tended to be longer in reactive hematopoietic marrow. Water signal ratio related to TE was significantly higher in reactive hematopoietic marrow. These results suggest a quantitative and qualitative difference in water components between normal and reactive hematopoietic bone marrow. (orig.)

  11. Tumour necrosis factor-alpha (TNFα stimulates the growth of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    F. Rougier

    1997-01-01

    Full Text Available This study reports that TNF-α is a potent mitogen for human bone marrow sternal cells in vitro (assessed by [3H]-thymidine incorporation into DNA and cell counts. In contrast, cytokines such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, LIF, SCF, M-CSF, G-CSF and GM-CSF had no effect. The effect of TNF-α on the growth of human bone marrow stromal cells could be of importance during inflammatory processes which take place in the marrow, for example marrow fibrosis.

  12. Increasing utilization of bone marrow transplantation. II. Results of the 1985-1987 survey.

    Science.gov (United States)

    Bortin, M M; Rimm, A A

    1989-09-01

    The International Bone Marrow Transplant REgistry conducts periodic surveys to determine activity in the field of allogeneic and syngeneic bone marrow transplantation. Data were reported to the IBMTR by 258 institutions in 41 countries regarding their patients who received bone marrow transplants during the period 1985-1987. To the best of our knowledge, the data represent essentially all bone marrow transplants (exclusive of autologous transplants) performed in the past 3 years. A total of 10,887 patients received bone marrow transplants; 73% were for leukemia, 11% for other malignant diseases, 9% for severe aplastic anemia and related disorders, 3% for immune deficiency diseases, 2% for thalassemia major, and 2% for genetic, metabolic, and several other rare diseases. 161 (62%) of the 258 institutions performed fewer than one transplant per month. More than 50% of the patients were transplanted in 37 institutions. 46% of the world's bone marrow transplants were performed in North America, 42% in Western Europe, 5% in Asia, 3% in Australia and New Zealand, 2% in the Mideast and Africa, 1% in South and Central America, and 1% in Eastern Europe and the USSR. The data reflect continued growth in utilization of allogeneic and syngeneic bone marrow transplantation and quantify the annual increases in the number of patients receiving transplants.

  13. In vivo cell kinetics of the bone marrow transplantation using dual colored transgenic rat system

    Science.gov (United States)

    Kai, Kotaro; Teraoka, Satoshi; Adachi, Yasushi; Ikehara, Susumu; Murakami, Takashi; Kobayashi, Eiji

    2008-02-01

    Because bone marrow is an adequate site for bone marrow stem cells, intra-bone marrow - bone marrow transplantation (IBM-BMT) is an efficient strategy for bone marrow transplantation (BMT). However, the fate of the transplanted cells remains unclear. Herein, we established a dual-colored transgenic rat system utilizing green fluorescent protein (GFP) and a luciferase (luc) marker. We then utilized this system to investigate the in vivo kinetics of transplanted bone marrow cells (BMCs) after authentic intravenous (IV)-BMT or IBM-BMT. The in vivo fate of the transplanted cells was tracked using an in vivo luminescent imaging technique; alterations in peripheral blood chimerism were also followed using flow cytometry. IBM-BMT and IV-BMT were performed using syngeneic and allogeneic rat combinations. While no difference in the proliferation pattern was observed between the two treatment groups at 7 days after BMT, different distribution patterns were clearly observed during the early phase. In the IBM-BMT-treated rats, the transplanted BMCs were engrafted immediately at the site of the injected bone marrow and expanded more rapidly than in the IV-BMT-treated rats during this phase. Graft-versus-host disease was also visualized. Our bio-imaging system using dual-colored transgenic rats is a powerful tool for performing quantitative and morphological assessments in vivo.

  14. CCR2 regulates the uptake of bone marrow-derived fibroblasts in renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Yunfeng Xia

    Full Text Available Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2 participates in the recruitment of fibroblasts into the kidney during the development of renal fibrosis. Bone marrow-derived collagen-expressing GFP⁺ fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted with donor bone marrow from collagen α1(I-GFP reporter mice. These bone marrow-derived fibroblasts expressed PDGFR-β and CCR2. CCR2 knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-β or procollagen I in the obstructed kidneys compared with wild-type mice. Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived myofibroblasts and expressed less α-SMA or FSP-1 in the obstructed kidneys compared with wild-type mice. Consistent with these findings, genetic deletion of CCR2 inhibited total collagen deposition and suppressed expression of collagen I and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16 gene expression associated with a reduction of inflammatory cytokine expression and macrophage infiltration, suggesting a linear interaction between two chemokines/ligand receptors in tubular epithelial cells. Taken together, our results demonstrate that CCR2 signaling plays an important role in the pathogenesis of renal fibrosis through regulation of bone marrow-derived fibroblasts. These data suggest that inhibition of CCR2 signaling could constitute a novel therapeutic approach for fibrotic kidney disease.

  15. Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology.

    Science.gov (United States)

    Siddiqui, A R; Oseas, R S; Wellman, H N; Doerr, D R; Baehner, R L

    1979-05-01

    Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer.

  16. Markers for Characterization of Bone Marrow Multipotential Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Boxall

    2012-01-01

    Full Text Available Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs, in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native bone marrow (BM MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1 may have the strongest translational value. Whereas small animal models are needed to discover the in vivo function on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

  17. Targeting the bone marrow: applications in stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Orchard, K. [Southampton University Hospital Trust, Southampton (United Kingdom). Department of Haematology; Cooper, M. [St. Bartholomew' s Hospital, London (United Kingdom). Pharmacy Department

    2004-12-01

    Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT.

  18. Saliva suppresses osteoclastogenesis in murine bone marrow cultures.

    Science.gov (United States)

    Caballé-Serrano, J; Cvikl, B; Bosshardt, D D; Buser, D; Lussi, A; Gruber, R

    2015-01-01

    Saliva can reach mineralized surfaces in the oral cavity; however, the relationship between saliva and bone resorption is unclear. Herein, we examined whether saliva affects the process of osteoclastogenesis in vitro. We used murine bone marrow cultures to study osteoclast formation. The addition of fresh sterile saliva eliminated the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase (TRAP). In line with the histochemical staining, saliva substantially reduced gene expression of cathepsin K, calcitonin receptor, and TRAP. Addition of saliva led to considerably decreased gene expression of receptor activator of nuclear factor kappa-B (RANK) and, to a lesser extent, that of c-fms. The respective master regulators of osteoclastogenesis (c-fos and NFATc1) and the downstream cell fusion genes (DC-STAMP and Atp6v0d2) showed decreased expression after the addition of saliva. Among the costimulatory molecules for osteoclastogenesis, only OSCAR showed decreased expression. In contrast, CD40, CD80, and CD86-all costimulatory molecules of phagocytic cells-were increasingly expressed with saliva. The phagocytic capacity of the cells was confirmed by latex bead ingestion. Based on these in vitro results, it can be concluded that saliva suppresses osteoclastogenesis and leads to the development of a phagocytic cell phenotype.

  19. Repair of segmental bone defects with bone marrow and BMP-2 adenovirus in the rabbit radius

    Science.gov (United States)

    Cheng, Lijia; Lu, Xiaofeng; Shi, Yujun; Li, Li; Xue, Jing; Zhang, Li; Xia, Jie; Wang, Yujia; Zhang, Xingdong; Bu, Hong

    2012-12-01

    Bone tissue engineering (BTE) is approached via implantation of autogenous mesenchymal stem cells (MSCs), marrow cells, or platelet-rich plasma, etc. To the contrary, gene therapy combining with the bone marrow (BM) has not been often reported. This study was performed to investigate whether a modified BTE method, that is, the BM and a recombinant human bone morphogenetic protein-2 adenovirus (Ad.hBMP-2) gene administering in hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics could accelerate the healing of segmental defects in the rabbit radius. In our study, ceramics were immersed in the adenovirus overnight, and half an hour before surgery, autologous BM aspirates were thoroughly mixed with the ceramics; at the same time, a 15-mm radius defect was introduced in the bilateral forelimbs of all animals, after that, this defect was filled with the following: (1) Ad.hBMP-2 + HA/β-TCP + autologous BM (group 1); (2) HA/β-TCP + Ad.hBMP-2 (group 2); (3) HA/β-TCP alone (group 3); (4) an empty defect as a control (group 4). Histological observation and μ-CT analyses were performed on the specimens at weeks 2, 4, 8, and 12, respectively. In group 1, new bone was observed at week 4 and BM appeared at week 12, in groups 2 and 3, new bone was observed at week 8 and it was more mature at week 12, in contrast, the defect was not bridged in group 4 at week 12. The new bone area percentage in group 1 was significantly higher than that in groups 2 and 3. Our study indicated that BM combined with hBMP-2 adenovirus and porous ceramics could significantly increase the amount of newly formed bone. And this modified BTE method thus might have potentials in future clinical application.

  20. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    Science.gov (United States)

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  1. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    Science.gov (United States)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  2. Bone marrow acid phosphatase by radioimmunoassay. [/sup 125/I; prostatic carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Belville, W.D.; Cox, H.D.; Mahan, D.E.; Olmert, J.P.; Mittemeyer, B.T.; Bruce, A.W.

    1978-06-01

    A double-antibody radioimmunoassay was developed and utilized to measure prostatic acid phosphatase in bone marrow aspirates. One hundred-eighteen patients with carcinoma of the prostate in various clinical stages, and fifty with benign prostatic hyperplasia were studied. In patients with carcinoma, levels of prostatic acid phosphatase in bone marrow aspirates were found to correlate well with increasing clinical stage of the disease. Determination of bone marrow prostatic acid phosphatase by radioimmunoassay may be a valuable adjunct to clinicopathologic staging of prostatic carcinoma.

  3. Ultrastructural changes of bone marrow cells exposed for xenogenous cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Shaymardanova L.R.

    2010-01-01

    Full Text Available Due to the scientifical investigations xenogenous cerebrospinal fluid was considered as possible substance for theproduction of powerful adaptogen of biological origin. One of the representative research in these field demonstrates morphologicaland functional changes of bone marrow as the central hemopoetic and immune organ. The article shows the ultramicroscopicchanges of bone marrow cells after the xenogenous cerebrospinal fluid exposure in Vistar rats of differentage. It was revealed the activation of synthetic processes in bone marrow cells of the first three age groups and exhaustion ofactivating mechanisms in the fourth age group, that was manifested in swelling and destruction of mytochondria, vacuolisationof cytoplasm, invagination of caryolemma.

  4. Bone marrow edema syndrome of the foot: one year follow-up with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Canton, Guillermo; Casado, Oscar; Capelastegui, Ana; Astigarraga, Elena; Larena, Jose Alejandro; Merino, Amaya [OSATEK, Unidades de Resonancia Magnetica, Dr. Areilza 12-16, 48011, Bilbao, Basque Country (Spain)

    2003-05-01

    To describe the MR findings of bone marrow edema syndrome (BMES) of the foot and its evolution at 1 year follow-up.Design and patients Twenty-five of 32 patients with disabling foot and ankle pain unrelated to trauma diagnosed as BMES when MR imaging demonstrated a bone marrow edema pattern in one or more bones without any radiological or underlying clinical cause, were re-evaluated by MR imaging 1 year later. On the initial MR examinations an average of 4.7 individual bones were involved by bone marrow edema. Soft tissue edema was present in every patient and joint effusion in 10 patients. MR imaging at 1 year showed resolution of bone edema in 18 patients (72%), partial improvement in five (20%) and no improvement in two (8%). Six patients (24%) developed similar symptoms in the other foot during follow-up. Ten of 17 available plain radiographs showed some loss of radiodensity. Further bone marrow edema developed in bones of the same foot that were initially normal, or in uninvolved distant bone marrow areas in the same affected bone, in six of seven patients on follow-up MR imaging. The evolution of the MR findings of BMES of the foot is to complete resolution or partial improvement at 1 year in the majority of cases. Migration to the other foot occurs in up to a quarter of patients. (orig.)

  5. Characterization of Fatty Acid Composition in Bone Marrow Fluid From Postmenopausal Women: Modification After Hip Fracture.

    Science.gov (United States)

    Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J; Seitz, Germán; Rodríguez, J Pablo

    2016-10-01

    Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65-80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. J. Cell. Biochem. 117: 2370-2376, 2016. © 2016 Wiley Periodicals, Inc.

  6. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT and 21 controls (CG. Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01. Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%. The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005, but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

  7. Bone marrow-derived dendritic cells pulsed with tumor lysates induce anti-tumor immunity against gastric cancer ex vivo

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS: c-kit+ hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNFα to induce their maturation. They were analysed by morphological observation, phenotype analysis, and mixed lymphocyte reaction (MLR). Bone marrow-derived DCs (BM-DCs) were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. Finally, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNy) secretion was evaluated ex vivo.RESULTS: c-kit+ hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs. Norphologically, observed by light microscope, these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, FACS analysis showed that they expressed.high levels of Ia, DEC-205, CD11b, CD80 and CD86 antigen, moderate levels of CD40, and negative for F4/80. Functionally, these ceils gained the capacity to stimulate allogeneic T cells in MLR assay. However, immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells. Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed (TP) DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T = 100:1, 69.55% ± 6.05% specific lysis), but not B16 tumor cells, and produced higher levels of IFNγ, when stimulated with SGC-7901 tumor cells but not when stimulated with B16 tumor cells (1575.31 ± 60.25 pg/mL in SGC-7901 group vs 164.11 ± 18.52 pg/mL in B16 group, P < 0.01).CONCLUSION: BM-derived DCs pulsed with tumor lysates can induce anti-tumor immunity specific to gastric cancer ex vivo.

  8. Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi;

    Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  9. Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  10. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure.

    Science.gov (United States)

    Fliedner, T M; Graessle, D; Paulsen, C; Reimers, K

    2002-08-01

    It is the purpose of this presentation to review the unique structure and function of bone marrow anchored hematopoiesis in their significance for its response mechanisms to an exposure to ionizing radiation. The ultimate objective of bone marrow hematopoiesis is to maintain in the peripheral blood a constant level of the different blood cell types (erythrocytes, granulocytes, platelets, lymphocytes, etc.). All of them have their particular turnover kinetics (such as granulocytes 120 x 10(9)/d, erythrocytes 200 x 10(9)/d or thrombocytes 150 x 10(9)/d), are semi-autonomous in their steady state regulatory mechanisms and dependent on a life-long supply of mature cells from a stem cell pool with unlimited replicative and pluripotent differentiative potential. The present knowledge of hematopoietic cellular renewal is the result of years of basic experimental and clinical studies using radionuclides in various metabolic forms including (59)Fe, (32)P (DF (32)P), (51)Cr, (131)I, (60)Co, (3)H ((3)HTdR) and (14)C ((14)CTdR). To understand the physiology but in particular the radiation-pathophysiology, it is essential to recognize in detail the infrastructure of the bone marrow as a distinct unit. Indispensable for a life-long cell production is the capsule of the marrow - the bone cortex -, the arterial supply of blood connected to the sinusoidal microvascular architecture with its sinusoids contorti and recti as well as the central (cell collecting) sinusoids. It is further of importance to recognize the significance of nerval regulation of blood flow, characterized by myelinated and unmyelinated nerve fibers. The type of unique lining cells of the sinusoids is the prerequisite for the cell traffic between the hemopoietic parenchyma and the blood. This in turn cannot be achieved without an alternative opening and closing of the sinusoidal segments which - in turn - requires a rigid long capsule to assure an - in toto - constant volume of each bone marrow unit. If a bone

  11. Long-term three-dimensional perfusion culture of human adult bone marrow mononuclear cells in bioreactors.

    Science.gov (United States)

    Schmelzer, Eva; Finoli, Anthony; Nettleship, Ian; Gerlach, Jörg C

    2015-04-01

    The construction and long-term maintenance of three-dimensional in vitro bone marrow models is of great interest but still quite challenging. Here we describe the use of a multi-compartment hollow-fiber membrane based three-dimensional perfusion bioreactor for long-term culture of whole human bone marrow mononuclear cells. We also investigated bioreactors with incorporated open-porous foamed hydroxyapatite scaffolds, mimicking the in vivo bone matrix. Cells in bioreactors with and without scaffolds were cultured to 6 weeks and compared to Petri dish controls. Cells were analyzed for gene expression, surface markers by flow cytometry, metabolic activity, hematopoietic potential, viability, and attachment by immunocytochemistry. Cells in bioreactors were metabolic active during long-term culture. The percentages of hematopoietic stem cell and mature endothelial cell fractions were maintained in bioreactors. The expression of most of the analyzed genes stabilized and increased after long-term culture of 6 weeks. Compared to Petri dish culture controls, bioreactor perfusion culture improved in both the short and long-term, the colony formation unit capacity of hematopoietic progenitors. Cells attached to the ample surface area provided by hydroxyapatite scaffolds. The implementation of a hydroxyapatite scaffold did not influence colony formation capacity, percentages of cell type specific fractions, gene expression, cell viability or metabolic turnover when compared to control cells cultured in bioreactors without scaffolds. In conclusion, three-dimensional perfusion bioreactor culture enables long-term maintenance of primary human bone marrow cells, with hydroxyapatite scaffolds providing an in vivo-like scaffold for three-dimensional culture.

  12. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-05-18

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.

  13. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Directory of Open Access Journals (Sweden)

    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  14. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Science.gov (United States)

    Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

    2014-01-01

    One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  15. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Science.gov (United States)

    Meier, Raphael P H; Seebach, Jörg D; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H; Muller, Yannick D

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  16. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  17. {sup 18}F-FDG PET/CT bone/bone marrow findings in Hodgkin's lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging

    Energy Technology Data Exchange (ETDEWEB)

    Moulin-Romsee, Gerard [Universite Paris 7, Service de Medicine Nucleaire, Hopital Saint-Louis, Assistance Publique-Hopitaux de Paris (France); Institut Curie, Nuclear Medicine, Paris (France); Hindie, Elif; Filmont, Jean-Emmanuel; Moretti, Jean-Luc [Universite Paris 7, Service de Medicine Nucleaire, Hopital Saint-Louis, Assistance Publique-Hopitaux de Paris (France); Cuenca, Xavier; Brice, Pauline; Sibon, David [Hopital Saint-Louis, Haemato-Oncology, Paris (France); Decaudin, Didier; Anitei, Marcela [Institut Curie, Haematology, Paris (France); Benamor, Myriam [Institut Curie, Nuclear Medicine, Paris (France); Briere, Josette [Hopital Saint-Louis, Pathology, Paris (France); Kerviler, Eric de [Hopital Saint-Louis, Radiology, Paris (France)

    2010-06-15

    Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. {sup 18}F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant {sup 18}F-FDG PET/CT. Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and {sup 18}F-FDG PET/CT. Results of BMB were not available at the time of {sup 18}F-FDG PET/CT imaging. Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on {sup 18}F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on {sup 18}F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy {sup 18}F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient. {sup 18}F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging. (orig.)

  18. Serum FLT-3 ligand in a busulphan-induced model of chronic bone marrow hypoplasia in the female CD-1 mouse.

    Science.gov (United States)

    Molyneux, Gemma; Gibson, Frances M; Whayman, Matthew; Turton, John A

    2008-04-01

    The concentration of the cytokine fms-like tyrosine kinase-3 ligand (FL) is elevated in the plasma of patients treated with chemotherapy or radiotherapy for malignant conditions. In addition, plasma FL is increased in patients with bone marrow failure resulting from stem-cell defects (e.g. aplastic anaemia). Our goal in the present study was to measure the concentration of serum FL in mice treated with the chemotherapeutic agent busulphan (BU) to induce bone marrow depression and relate changes in FL to effects on haemopoiesis. Female CD-1 mice were treated with BU (9.0 mg/kg) or vehicle by intraperitoneal injection on 10 occasions over 21 days. Animals were autopsied on days 1, 23, 72, 119 and 177 postdosing. A full blood count was performed, and serum prepared for FL analysis. Femoral marrow cell suspensions were prepared to assess the total femoral nucleated cell count (FNCC) and the number of committed haemopoietic progenitor cells (CFU-C). On days 1 and 23 postdosing, significant decreases were evident in many peripheral blood parameters; the FNCC and CFU-C were also reduced in BU-treated mice, in conjunction with increases in serum FL levels. On days 72, 119 and 177 postdosing, several peripheral blood and bone marrow parameters remained reduced and the concentration of serum FL continued to be significantly increased. Linear regression analysis demonstrated significant correlations between the concentration of serum FL in BU-treated mice and peripheral blood and bone marrow parameters; this suggests the possible use of serum FL as a potential biomarker for drug-induced bone marrow injury.

  19. Assessment of bone marrow changes in postmenopausal women with varying bone densities: magnetic resonance spectroscopy and diffusion magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; TANG Guang-yu; TANG Rong-biao; PENG Yi-feng; LI Wei

    2010-01-01

    Background Recent studies suggest that bone marrow adipose tissue might play a role in the pathogenesis of osteoporosis. There are inconsistent findings on the relationship among marrow fat content, bone mineral density and apparent diffusion coefficient (ADC). This study aimed to prospectively explore the efficacy of MR spectroscopy (MRS)and diffusion-weighted MR imaging (DWI) in detecting vertebral marrow changes in postmenopausal women with varying bone densities.Methods Both MRS and DWI of the lumber spine were performed in 102 postmenopausal women (mean age,(67.3±6.5) years; range, 55-83 years), who underwent dual X-ray absorptiometry. Marrow fat content and ADC were compared and correlated among three groups: 24 with normal bone density, 31 with osteopenia and 47 with osteoporosis.Results Vertebral marrow fat content was significantly increased in the osteoporotic group ((65.60±7.68)%, P <0.001)and the osteopenic group ((57.68±6.45)%, P <0.001), when compared with the normal bone density group ((51.67±3.27)%). ADC values were significantly decreased in the osteoporotic group ((0.39±0.03)×10-3mm2/s, P <0.001)and in the osteopenic group ((0.42±0.02)×10-3mm2/s, P <0.001), when compared with the normal bone density group ((0.47±0.03)×10-3 mm2/s). The marrow fat content negatively correlated with both bone density (r=-0.731, P <0.001)and marrow ADC (r=-0.572, P <0.001). The bone density positively correlated with the ADC values (r=0.802, P<0.001).Conclusions Postmenopausal women experience a corresponding increase in vertebral marrow fat content as the bone density decreases. Marrow fat content and ADC correlate to the bone density. MRS and DWI may indirectly assess the early bone marrow changes in postmenopausal women.

  20. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Science.gov (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.

  1. In vivo osteoinductive effect and in vitro isolation and cultivation bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Redzić, Amira; Smajilagić, Amer; Aljicević, Mufida; Berberović, Ljubomir

    2010-12-01

    Bone marrow contains cell type termed mesenchymal stem cells (MSC), first recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That MSCs have potential to differentiate in vitro in to the various cells lines as osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study were to show in vivo capacity of bone marrow MSC to produce bone in surgically created non critical size mandible defects New Zeland Rabbits, and then in second part of study to isolate in vitro MSC from bone marrow, as potential cell transplantation model in bone regeneration. In vivo study showed new bone detected on 3D CT reconstruction day 30, on all 3 animals non critical size defects, treated with bone marrow MSC exposed to the human Bone Morphogenetic Protein 7 (rhBMP-7). Average values of bone mineral density (BMD), was 530 mg/cm3, on MSC treated animals, and 553 mg/cm3 on control group of 3 animals where non critical size defects were treated with iliac crest autologue bone graft. Activity of the Alkaline Phosphatase enzyme were measurement on 0.5, 14, 21, 30 day and increased activity were detected day 14 on animals treated with bone marrow MSCs compared with day 30 on iliac crest treated animals. That results indicates strong osteoinduction activity of the experimental bone marrow MSCs models exposed to the rhBMP-7 factor Comparing ALP activity, that model showed superiorly results than control group. That result initiates us in opinion that MSCs alone should be alternative for the autolologue bone transplantation and in vitro study we isolated singles MSCs from the bone marrow of rat's tibia and femora and cultivated according to the method of Maniatopoulos et all. The small initial colonies of fibroblast like cells were photo-documented after 2 days of primary culture. Such isolated and cultivated MSCs in future studies will be exposed to the growth factors to differentiate in osteoblast and indicate their clinically potential as alternative

  2. Citalopram increases the differentiation efifcacy of bone marrow mesenchymal stem cells into neuronal-like cells

    Institute of Scientific and Technical Information of China (English)

    Javad Verdi; Seyed Abdolreza Mortazavi-Tabatabaei; Shiva Sharif; Hadi Verdi; Alireza Shoae-Hassani

    2014-01-01

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

  3. Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

    Directory of Open Access Journals (Sweden)

    Muccioli Cristina

    2002-01-01

    Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

  4. Histological study of granulocytic series in the bone marrow of adult goat (Caprus Hircus

    Directory of Open Access Journals (Sweden)

    Yahia Dahash Hamdi

    2016-09-01

    Conclusion The developmental process of granulocytopioesis series of bone marrow in goat encompasses a lineage of successive morphological alterations involves nuclear and cytoplasmic changes as well as granule transformation resulting in the production of granulocytes.

  5. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Fatemeh Anbari; Mohammad Ali Khalili; Ahmad Reza Bahrami; Arezoo Khoradmehr; Fatemeh Sadeghian; Farzaneh Fesahat; Ali Nabi

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intrave-nous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and ad-ministered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significant-ly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  6. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  7. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    I. A. Lisukov

    2014-07-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  8. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    I. A. Lisukov

    2012-01-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  9. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  10. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    Science.gov (United States)

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  11. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

  12. Hypercapnia slows down proliferation and apoptosis of human bone marrow promyeloblasts.

    Science.gov (United States)

    Hamad, Mouna; Irhimeh, Mohammad R; Abbas, Ali

    2016-09-01

    Stem cells are being applied in increasingly diverse fields of research and therapy; as such, growing and culturing them in scalable quantities would be a huge advantage for all concerned. Gas mixtures containing 5 % CO2 are a typical concentration for the in vitro culturing of cells. The effect of varying the CO2 concentration on promyeloblast KG-1a cells was investigated in this paper. KG-1a cells are characterized by high expression of CD34 surface antigen, which is an important clinical surface marker for human hematopoietic stem cells (HSCs) transplantation. KG-1a cells were cultured in three CO2 concentrations (1, 5 and 15 %). Cells were batch-cultured and analyzed daily for viability, size, morphology, proliferation, and apoptosis using flow cytometry. No considerable differences were noted in KG-1a cell morphological properties at all three CO2 levels as they retained their myeloblast appearance. Calculated population doubling time increased with an increase in CO2 concentration. Enhanced cell proliferation was seen in cells cultured in hypercapnic conditions, in contrast to significantly decreased proliferation in hypocapnic populations. Flow cytometry analysis revealed that apoptosis was significantly (p = 0.0032) delayed in hypercapnic cultures, in parallel to accelerated apoptosis in hypocapnic ones. These results, which to the best of our knowledge are novel, suggest that elevated levels of CO2 are favored for the enhanced proliferation of bone marrow (BM) progenitor cells such as HSCs.

  13. Membrane lipid rafts, master regulators of hematopoietic stem cell retention in bone marrow and their trafficking.

    Science.gov (United States)

    Ratajczak, M Z; Adamiak, M

    2015-07-01

    Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein microdomains, known as lipid rafts, which float freely in the membrane bilayer. These structures have an important role in assembling signaling molecules (e.g., Rac-1, RhoH and Lyn) together with surface receptors, such as the CXCR4 receptor for α-chemokine stromal-derived factor-1, the α4β1-integrin receptor (VLA-4) for vascular cell adhesion molecule-1 and the c-kit receptor for stem cell factor, which together regulate several aspects of hematopoietic stem/progenitor cell (HSPC) biology. Here, we discuss the role of lipid raft integrity in the retention and quiescence of normal HSPCs in bone marrow niches as well as in regulating HSPC mobilization and homing. We will also discuss the pathological consequences of the defect in lipid raft integrity seen in paroxysmal nocturnal hemoglobinuria and the emerging evidence for the involvement of lipid rafts in hematological malignancies.

  14. TGF-β Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia.

    Science.gov (United States)

    Zhang, Haojian; Kozono, David E; O'Connor, Kevin W; Vidal-Cardenas, Sofia; Rousseau, Alix; Hamilton, Abigail; Moreau, Lisa; Gaudiano, Emily F; Greenberger, Joel; Bagby, Grover; Soulier, Jean; Grompe, Markus; Parmar, Kalindi; D'Andrea, Alan D

    2016-05-05

    Fanconi anemia (FA) is an inherited DNA repair disorder characterized by progressive bone marrow failure (BMF) from hematopoietic stem and progenitor cell (HSPC) attrition. A greater understanding of the pathogenesis of BMF could improve the therapeutic options for FA patients. Using a genome-wide shRNA screen in human FA fibroblasts, we identify transforming growth factor-β (TGF-β) pathway-mediated growth suppression as a cause of BMF in FA. Blocking the TGF-β pathway improves the survival of FA cells and rescues the proliferative and functional defects of HSPCs derived from FA mice and FA patients. Inhibition of TGF-β signaling in FA HSPCs results in elevated homologous recombination (HR) repair with a concomitant decrease in non-homologous end-joining (NHEJ), accounting for the improvement in cellular growth. Together, our results suggest that elevated TGF-β signaling contributes to BMF in FA by impairing HSPC function and may be a potential therapeutic target for the treatment of FA.

  15. From Adult Bone Marrow Cells to Other Cell Lineages:Transdifferentiation or Cells Fusion

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Recent studies have demonstrated that intravenous transplantation or local injection of bone marrow cells can induce unexpected changes of their fate. The results of these experiments showed that after transplantation or injecton, some of tissue specific somatic cells such as hepatocytes, skeleton, cardiac muscle cells and brain cells expressed the donor cell-specific genes, such as Y chromosome. There are two hypotheses that can explain this phenomenon. One is bone marrow stem cell transdifferentiation and the other is spontaneous cell fusion.

  16. Bone marrow edema of the knee joint; Differenzialdiagnosen des Knochenmarkoedems am Kniegelenk

    Energy Technology Data Exchange (ETDEWEB)

    Breitenseher, M.J. [Waldviertelklinikum Horn (Austria). Institut fuer Radiologie; Universitaetsklinik fuer Radiodiagnostik Wien (Austria). Abteilung Osteologie; Kramer, J. [Institut fuer CT- und MRT-Diagnostik, Linz (Austria); Mayerhoefer, M.E. [Universitaetsklinik fuer Radiodiagnostik Wien (Austria). Abteilung Osteologie; Aigner, N. [Orthopaedisches Krankenhaus Speising, Erste Orthopaedische Abteilung, Wien (Austria); Hofmann, S. [LKH Stolzalpe (Austria). Orthopaedische Abteilung

    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.) [German] Das Knochenmarkoedem des Kniegelenks ist ein haeufiges Erscheinungsbild in der MR-Diagnostik. Es kann mit Symptomen und Schmerzen des Gelenks einhergehen. Erkrankungen, die mit einem Knochenmarkoedem vergesellschaftet sind, koennen in verschiedene Gruppen eingeteilt werden. Zur 1. Gruppe gehoeren das vaskulaer-ischaemische Knochenmarkoedem mit Osteonekrose (Synonyme SONK oder Morbus Ahlbaeck), die Osteochondrosis dissecans und das Knochenmarkoedemsyndrom, zur 2. Gruppe das traumatologische oder mechanische Knochenmarkoedem. In der 3. Gruppe werden reaktive Knochenmarkoedeme zusammengefasst wie bei Gonarthrose, postoperative Knochenmarkoedeme und reaktive Oedeme bei Tumor oder tumoraehnlichen Erkrankungen. Der Nachweis eines Knochenmarkoedems gelingt mit der MRT sehr sensitiv, die rein morphologische MR-Information ist jedoch oft unspezifisch, sodass anamnestische und klinische Informationen fuer die sichere Zuordnung einer Erkrankung in den meisten Faellen notwendig sind. (orig.)

  17. Thalassemia paravertebral tumors and bone marrow scan; Thalassemies, tumeurs paravertebrales et scintigraphie medullaire

    Energy Technology Data Exchange (ETDEWEB)

    Huglo, D.; Rose, C.; Deveaux, M.; Bauters, F.; Marchandise, X. [Centre Hospitalier Universitaire, 59 - Lille (France)

    1995-12-01

    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{sup -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.

  18. Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

    OpenAIRE

    Claudia Momo; Ana Paula Prudente Jacintho; Pamela Rodrigues Reina Moreira; Danísio Prado Munari; Gisele Fabrino Machado; Rosemeri Oliveira Vasconcelos

    2014-01-01

    The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eos...

  19. Sickle-β+ thalassemia with splenic calcification and bone marrow infarction: a case report

    OpenAIRE

    2008-01-01

    We came across an unusual case of a 20 years old male from north India who presented with repeated episodes of pyrexia of unknown origin (PUO) and history of chronic hemolytic anemia. On investigation he was detected to have Sickle-β+ Thalassemia and subtle features of hyposplenism. Radiological investigations revealed extensive splenic calcification and bone marrow examination to evaluate for PUO showed extensive bone marrow infarction and fibrosis. Molecular diagnosis for beta thalassemia m...

  20. Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Bourbonniere, Lyne; Hassan-Zahraee, Mina;

    2004-01-01

    . These discrepancies may reflect balance between immunoregulatory and neurocytopathologic roles for NO. We investigated selective effects of bone marrow-derived versus CNS parenchymal sources of iNOS in EAE in chimeric mice. Chimeras that selectively expressed or ablated iNOS in leukocytes both showed significant...... delay in disease onset, with no difference in disease severity. We conclude that bone marrow-derived and CNS parenchymal sources of iNOS-derived NO both play a regulatory role in EAE....