Abstract:
:An evaluation of the effectiveness of a genetically engineered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3) fusion protein (FP) as a means of delivering cytokine combinations to megakaryocyte (MK) progenitor cells was performed, utilizing a serum-depleted clonal assay system and a long-term bone marrow culture system. The effects of the FP, alone and in combination with a variety of other cytokines, on the primitive MK progenitor cell, the megakaryocyte burst-forming unit (BFU-MK), and the more differentiated megakaryocyte colony-forming unit (CFU-MK) were assessed. Subpopulations of bone marrow cells (CD34+ DR- for BFU-MK and CD34+ DR+ for CFU-MK) served as sources of these two classes of MK progenitor cells. The FP was equivalent to a combination of optimal concentrations of GM-CSF and IL-3 in promoting both the number and size of BFU-MK-derived colonies. The GM-CSF/IL-3 combination, however, promoted the formation of far greater CFU-MK-derived colonies than did the FP alone. The size of MK colonies formed in the presence of the FP or GM-CSF/IL-3 was similar. The ability of the FP to stimulate BFU-MK- but not CFU-MK-derived colony formation was also further augmented by the addition of interleukin 1 alpha (IL-1 alpha). The addition of c-kit ligand (KL) increased both FP-stimulated CFU-MK- and BFU-MK-derived colony numbers but only BFU-MK-derived colony size. In addition, the FP alone sustained long-term megakaryocytopoiesis in vitro to a level equivalent to that of the GM-CSF/IL-3 combination and was superior in this regard to either GM-CSF or IL-3 alone. These data indicate that FP is capable of supporting various stages of human megakaryocytopoiesis. We conclude that such genetically engineered molecules as the FP may prove to be effective means of pharmacologically delivering the biological effects of specific cytokine combinations.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Bruno E,Briddell RA,Cooper RJ,Brandt JE,Hoffman Rkeywords:
subject
Has Abstractpub_date
1992-05-01 00:00:00pages
494-9issue
4eissn
0301-472Xissn
1873-2399journal_volume
20pub_type
杂志文章abstract::A modification of the fluorescence-activated cell sorter (FACS) was used to rapidly and reliably study the clonal proliferation of single hemopoietic cells. Murine FDC-P1 and human cord blood progenitor cells were examined for their ability to proliferate from single cells in 96-well microtiter plates containing agar ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::A modified regimen of high-dose cyclophosphamide (CTX) plus cyclosporine (CsA) was adopted for patients with severe or very severe aplastic anemia, and the effectiveness was compared with a regimen of antithymocyte globulin (ATG) plus CsA. A total of 121 patients enrolled in this study received either CTX plus CsA (CT...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2013.01.001
更新日期:2013-04-01 00:00:00
abstract::It is a well recognized problem that sample derived transferrin-bound iron (Tf-Fe) interferes with radio-iron incorporation into heme in the in vitro assay of erythropoietin (Ep) using fetal mouse liver cells (FMLC). This paper describes a mathematical procedure to correct for the unknown quantity of "cold" Tf-Fe in a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract::Fractionated whole body irradiation induces thymic lymphomas in C57 BL/Ka mice after 6-12 months. A graft of normal congenic bone marrow cells immediately after the last irradiation prevents the development of lymphomas by inducing the disappearance of preleukemic cells. When such a graft is performed one month later,...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.12.003
更新日期:2016-04-01 00:00:00
abstract::The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34 hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had we...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::We established a clonal cell culture system for human natural killer (NK) cells from fetal thymocytes. Thymocytes of 16 to 22 gestational weeks were cultured in methylcellulose in the presence of interleukin (IL)-7, IL-15, and steel factor (SF). After 14 days in incubation, large, diffuse colonies consisting of small ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00005-3
更新日期:1999-04-01 00:00:00
abstract::An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Differentiation- and lineage-related differences in the expression of two anti-apoptotic molecules, bcl-x and bcl-2, were examined using various human hematopoietic cell lines. Bcl-x was strongly expressed in cell lines with erythroid and megakaryocytic properties (K562, HEL, CMK, and Mo7E), and was moderately express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract:OBJECTIVE:Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their antiinflammatory/immune modulatory effects. MATERIALS AND ME...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.004
更新日期:2009-12-01 00:00:00
abstract::Radiation damage to femoral hemopoietic stroma in mice was measured 6 weeks after irradiation and reconstitution with syngeneic bone marrow by quantitation of fibroblastic progenitor cells (CFUF), and by assaying hemopoietic progenitors and CFUF numbers in regenerated subcutaneous femur implants. A dose-dependent effe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract::A functional method for estimation of plasminogen activator (PA) activity is described. The end-point method follows the PA-dependent conversion of the inactive plasminogen to the potent protease plasmin. The formation of plasmin is monitored by its activity on 14C-globin to form acid-soluble radioactive products. The...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::HIV-derived lentiviral vectors have been used widely to transduce non-dividing cells, such as hematopoietic stem cells (HSCs), in the setting of gene therapy. In this study, we screened lentiviral vectors for their ability to drive expression of the murine MHC class II chaperone, invariant chain (Ii) and a GFP reporte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.07.002
更新日期:2013-11-01 00:00:00
abstract::In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract:OBJECTIVE:Multipotent germline stem (mGS) cells derived from neonatal mouse testis, similar to embryonic stem (ES) cells, differentiate into various types of somatic cells in vitro and produce teratomas after inoculation into mice. In the present work, we examined mGS cells for hematopoietic progenitor potential in vit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.006
更新日期:2009-12-01 00:00:00
abstract::Graft-versus-host disease (GVHD), mediated by donor-derived alloreactive T cells, is a major cause of nonrelapse mortality in allogeneic hematopoietic stem cell transplantation. Its therapy is not well-defined. We established allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies (ASHmAbs) that speci...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.10.008
更新日期:2015-02-01 00:00:00
abstract::The origin of spleen colony-forming units (CFUs) and fibroblastoid colony-forming cells (CFUF) repopulating the marrow of femurs subcutaneously implanted in syngeneic and semi-syngeneic mice was studied by making use of a chromosome marker for CFUs and a cytotoxicity test for CFUF. The CFUs present in implants during ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal me...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2016.12.007
更新日期:2017-04-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::It is known that inadequate erythropoietin (EPO) production contributes to the pathogenesis of anemia of inflammation, although the exact molecular mechanism is unknown. Aryl hydrocarbon receptor (AhR) may compete with hypoxia-inducible factor 2α (HIF-2α), the master regulator of EPO production, for binding with HIF-1...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.08.010
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVE:Clonal stem cell proliferation and increased erythrocyte mass are hallmarks of the myeloproliferative disorder polycythemia vera (PV). The molecular basis of PV is unknown. METHODS:We carried out a genome-wide screening for loss of heterozygosity (LOH) and analyzed candidate genes within the LOH loci. RESUL...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00789-5
更新日期:2002-03-01 00:00:00
abstract::The development of a hematopoietic reporter is crucial for determining the fate of lineages derived from cell-based therapies. A marking system will enable safer embryonic stem and induced pluripotent stem cell-based derivation of blood lineages and facilitate the development of efficient cellular reprogramming strate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.05.005
更新日期:2014-09-01 00:00:00
abstract::Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found ins...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.010
更新日期:2016-05-01 00:00:00
abstract::We detail a novel, sensitive, and reproducible in vitro bioassay for erythropoietin that can be performed conveniently in any laboratory and is well suited for analysis of large numbers of samples. The assay measures DNA synthesis by a cohort of highly erythropoietin-responsive red cell precursors appearing in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Many granulocyte-specific mouse monoclonal antibodies recognize the carbohydrate sequence 3-fucosyllactosamine, Ga 1 beta 1-4[Fuc alpha 1-3]GlcNAc, which occurs in cell-surface glycolipids and glycoproteins. In general, these antibodies bind to blast cells from most patients with acute myeloblastic leukemia, but not t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Allogeneic bone marrow recipients exhibit a complex and multifactorial immunodeficiency affecting numerous effector functions for various periods of time. In order to evaluate their Fc-mediated monocyte-macrophage (MM) function we studied the clearance of IgG-coated Rh-positive erythrocytes (EA) in healthy control sub...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00
abstract:OBJECTIVE:The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environm...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.11.011
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.030
更新日期:2007-04-01 00:00:00
abstract::Previous studies have suggested that in vivo granulocyte colony-stimulating factor (G-CSF) pharmacokinetics may change over time. We studied three patients treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) for metastatic breast cancer after intravenous administration of reco...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00