Abstract：
OBJECTIVE:Strategies to expand hematopoietic stem cells (HSCs) ex vivo are of key interest. The objective of this study was to resolve if ability of HOXB4, previously documented to induce a significant expansion of HSCs in culture, may extend to other HOX genes and also to further analyze the HOX sequence requirements to achieve this effect. METHODS:To investigate the ability of Nucleoporin98-Homeobox fusion genes to stimulate HSC self-renewal, we evaluated their presence in 10- to 20-day cultures of transduced mouse bone marrow cells. Stem cell recovery was measured by limiting-dilution assay for long-term competitive repopulating cells (CRU Assay). RESULTS:These experiments revealed remarkable expansions of Nucleoporin98-Homeobox-transduced HSCs (1000-fold to 10,000-fold over input) in contrast to the expected decline of HSCs in control cultures. Nevertheless, the Nucleoporin98-Homeobox-expanded HSCs displayed no proliferative senescence and retained normal lympho-myeloid differentiation activity and a controlled pool size in vivo. Analysis of proviral integration patterns showed the cells regenerated in vivo were highly polyclonal, indicating they had derived from a large proportion of the initially targeted HSCs. Importantly, these effects were preserved when all HOX sequences flanking the homeodomain were removed, thus defining the homeodomain as a key and independent element in the fusion. CONCLUSION:These findings create new possibilities for investigating HSCs biochemically and genetically and for achieving clinically significant expansion of human HSCs.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Ohta H,Sekulovic S,Bakovic S,Eaves CJ,Pineault N,Gasparetto M,Smith C,Sauvageau G,Humphries RKdoi
10.1016/j.exphem.2007.02.012subject
Has Abstractpub_date
2007-05-01 00:00:00pages
817-30issue
5eissn
0301-472Xissn
1873-2399pii
S0301-472X(07)00118-Xjournal_volume
35pub_type
杂志文章abstract：:Among 75 consecutive allogeneic bone marrow transplant recipients, 24 developed chronic graft-versus-host disease (GVHD), which was diagnosed from day 31 to day 368 after transplantation. Eight (33%) patients had more extensive chronic GVHD, and five patients died. The actuarial incidence of chronic GVHD was 48% at 40...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:It has been demonstrated that genomic alterations of cells in the hematopoietic microenvironment could induce myelodysplastic syndromes (MDS) with ineffective hematopoiesis and dysmorphic hematopoietic cells, and subsequent transformation to acute myeloid leukemia. This investigation is the first attempt to correlate ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.10.009
更新日期：2013-02-01 00:00:00
abstract：:Peritoneal injection of thioglycollate medium (TM) to mice results in a dramatic increase in total number of peritoneal macrophages within 48 to 72 hours. Unlike resident macrophages, a fraction (10 to 20%) of these newly arrived young macrophages, designated as macrophage colony-forming cells (M-CFC), are highly prol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-10-01 00:00:00
abstract：:The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00031-9
更新日期：1999-02-01 00:00:00
abstract：OBJECTIVE:The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. MATERIALS AND METHODS...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2003.08.016
更新日期：2003-12-01 00:00:00
abstract：:The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony-stimulating factor (G-CSF) promptly engraft allogeneic recipients after myeloablative chemotherapy for hematologic malignancies. Surprisingly, no exacerbation of acute graft-vs-host disease has been observed despite a 10-fold higher T-cell conten...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00617-8
更新日期：2001-04-01 00:00:00
abstract：:Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the d...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.12.008
更新日期：2018-04-01 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：:The effect of recombinant interleukin 3 (IL-3) on the function of murine resident peritoneal macrophages was investigated. IL-3 enhanced the phagocytosis of Candida pseudotropicalis and Candida albicans and enhanced killing of the former. The enhanced killing is inhibited by scavengers of oxygen radicals, suggesting t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：OBJECTIVE:To study the early time course of engraftment of human mesenchymal stem cells in fetal sheep heart and determine the relative roles of proliferation and homing in formation of aggregates of human Purkinje fiber cells. METHODS:The human sheep xenograft model was utilized for these studies. Prior to injection ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.019
更新日期：2006-07-01 00:00:00
abstract：:Histone deacetylase inhibitors (HDACIs) have demonstrated effectiveness against lymphomas and myelomas in clinical practice. However, common to all currently approved broad-acting HDACIs (panHDACIs) is dose-limiting thrombocytopenia, which has prevented wider use in cancer therapy. Using CD34+ hematopoietic stem cells...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.12.007
更新日期：2019-04-01 00:00:00
abstract：:Time-lapse cinemicroscopy was used to observe the development of lymphocyte colonies in a phytohemagglutinin-dependent one-step, two-layer agar culture system. More than 1000 h of culture time were recorded in a total of 14 independent experiments. Blast formation and organization of lymphocytes into highly motile pai...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 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：:It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific poly...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.11.005
更新日期：2014-03-01 00:00:00
abstract：:The aberrant overexpression of Wilms tumor-1 (WT1) in acute myeloid leukemia (AML) plays an important role in blast cell survival by enhancing proliferation and inhibiting apoptosis. However, the mechanism underlying the overexpression of WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600 targ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.02.001
更新日期：2018-05-01 00:00:00
abstract：OBJECTIVE:Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS:Human myeloid ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00626-9
更新日期：2001-05-01 00:00:00
abstract：:Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published in peer-reviewed jou...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2008.01.010
更新日期：2008-06-01 00:00:00
abstract：:The extent of incorporation of bromodeoxyuridine (BrdUrd) into DNA of different types of hematopoietic stem cells assayed in vivo and of progenitor cells assayed in vitro was determined after continuous infusion of BrdUrd into mice for either four or seven days. Cells surviving subsequent exposure to 320 nm ultraviole...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development. MATERIALS AND METHODS:Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00128-9
更新日期：2000-01-01 00:00:00
abstract：:A useful cytochemical technique has been developed which facilitates the identification of the types of cell aggregates which proliferate in soft agar cultures of hematopoietic stem cells. Staining of fixed agar discs for alpha-naphthyl acetate esterase (ANAE), naphthol AS-D chloroacetate esterase (CAE) and with Luxol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：OBJECTIVE:Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR) and shows a broad spectrum of cytotoxic effects against human cancer cells. In order to enhance these effects, we introduced additional hydroxyl moieties into t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.05.018
更新日期：2006-10-01 00:00:00
abstract：:During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.03.002
更新日期：2010-06-01 00:00:00
abstract：:Improving our understanding of the intricacies of hematopoietic specification of induced or embryonic human pluripotent stem cells is beneficial for many areas of research and translational medicine. Currently, it is not clear whether, during human pluripotent stem cells hematopoietic differentiation in vitro, the mat...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.05.007
更新日期：2018-09-01 00:00:00
