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 capacity. MATERIALS AND METHODS:Sheep were transplanted with hESC-derived CD34(+) cells, as well as nonsorted differentiated cultures. Transplantations were carried out with in utero intraperitoneal injections prior to development of the immune system in the fetus so that tolerance toward foreign antigens was acquired during gestation and persisted in the adult. RESULTS:All cell populations that were tested demonstrated human cellular activity and long-term presence up to 5 years. However, the in vivo beta-cell-like activity achieved from the transplantation of the sorted CD34(+) cell population was not augmented by transplanting the entire cell population from which the CD34(+) cells were isolated. Human DNA and insulin messenger RNA were detected in sheep pancreases. An average of 1.51 ng/mL human C-peptide was detected in serum from eight animals transplanted with differentiated cell populations and assayed up to 55 months posttransplantation. Transplantation of as few as 23,500 cells resulted in long-term sustainable beta-cell-like activity. Teratomas were absent in the transplanted animals. CONCLUSION:Our data suggest that hESC-derived CD34(+) cells have a potential for long-term in vivo endocrine cellular activity that could prove useful in regenerative medicine. Because the same cell population has previously been shown to contain hematopoietic potential, it could be used for the induction of immunological tolerance and bone marrow chimerism prior to cellular therapy for diabetes.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Goodrich AD,Ersek A,Varain NM,Groza D,Cenariu M,Thain DS,Almeida-Porada G,Porada CD,Zanjani EDdoi
10.1016/j.exphem.2010.03.002subject
Has Abstractpub_date
2010-06-01 00:00:00pages
516-525.e4issue
6eissn
0301-472Xissn
1873-2399pii
S0301-472X(10)00079-2journal_volume
38pub_type
杂志文章abstract::Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hemato...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.09.006
更新日期:2009-01-01 00:00:00
abstract::Previous studies have suggested that Steel factor (SF) can influence the behavior of many types of hematopoietic progenitor cells both in vivo and in vitro, although whether these may include the most primitive populations of totipotent repopulating cells remains controversial. To approach this question, we measured t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential h...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-05-01 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:OBJECTIVE:T lymphocytes can be activated by soluble factors such as cytokines or through direct cell-cell interactions. Although cytokine receptors are known to signal through STAT family transcription factors, the mechanisms by which other cell-surface molecules, such as CD2, transduce signals is unclear. The goal of ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00652-4
更新日期:2001-02-01 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:OBJECTIVE:It is well known that hypoxic stress strongly enhances erythropoiesis, but the effect of hypoxia on erythroid progenitors has not been examined precisely. In the present study, using the erythropoietin-dependent cell line UT-7/Epo, which has characteristics of erythroid progenitors, we investigated a novel ro...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.01.013
更新日期:2005-05-01 00:00:00
abstract::Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data sh...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::To characterize hematopoietic cell biology, many investigators have used protocols that enrich for primitive hematopoietic stem cells (PHSC). In this study, we quantified the long-term repopulating ability (LTRA) of enriched and discarded fractions of PHSC from day-14 murine fetal liver using the competitive repopulat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Patients with cytopenias and a cellular bone marrow can be a diagnostic and therapeutic challenge. Previous reports suggested a role for progenitor assays for diagnosis and predicting response to therapy. We report the results of Burst-forming unit-erythroid (BFU-E) assays in 48 consultative cases of single or multili...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2013.04.013
更新日期:2013-09-01 00:00:00
abstract::We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract:OBJECTIVE:The ABCG2 transporter has been identified as a determinant of the side population (SP) in murine bone marrow and a potential marker for primitive stem cells. To assess the potential of the SP phenotype and ABCG2 expression to identify stem cells in human umbilical cord blood (hUCB), we have examined directly ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.09.015
更新日期:2009-02-01 00:00:00
abstract::Distinctive patterns of chromatin modification control gene expression and define cellular identity during development and cell differentiation. Polycomb repressive complex 2 (PRC2), the sole mammalian enzymatic complex capable of establishing gene-repressive high-degree methylation of histone H3 at lysine 27 (H3K27),...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.001
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:B-lineage acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphatic blastic phase in adults have poor prognoses despite intensive chemotherapy. Novel targeted treatment modalities emerge, but their evaluation requires relevant in vitro models of lymphoblastic leukemia. Presently available c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.11.002
更新日期:2009-03-01 00:00:00
abstract::Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental con...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::The proliferative capacity of partially purified populations of mouse bone marrow progenitor cells has been examined in serum-free cultures in the presence and absence of colony-stimulating factors (CSFs). The half-life of progenitor cells was approximately 25 h in the absence of factor, regardless of whether the fact...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 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::Cells for study were obtained from mouse bone marrow by three methods: 1) Mechanical dissociation; 2) Trypsin release; and 3) Passage through a syringe and needle. The ratio of the fibroblast colony-forming cells in these suspensions was, respectively, 1:13:1. Of the colonies formed by cells obtained by trypsin releas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::We have studied the ability of subpopulations of hemopoietic stem cells, obtained from murine bone marrow using elutriation and multiparameter sorting, to establish and maintain hemopoiesis following their deposition on irradiated stromal layers of long-term bone marrow cultures. Two fractions were obtained that diffe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00868-8
更新日期:2002-09-01 00:00:00
abstract:OBJECTIVE:Recruitment of endothelial progenitor cells to the sites of ischemia has recently been suggested as a mechanism of tissue repair. Here we address the hypothesis that the hypoxia-inducible full-length endothelial-monocyte-activating polypeptide II (EMAP II) provides a mechanism to recruit late outgrowth highly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.021
更新日期:2006-08-01 00:00:00
abstract::A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract:OBJECTIVE:Our laboratory reported that the angiotensin converting enzyme inhibitor captopril improves erythroid recovery from total body irradiation (TBI) in mice when administered after irradiation. However, captopril administered before TBI attenuates erythroid recovery. Here we investigate captopril and radiation re...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.12.002
更新日期:2011-03-01 00:00:00
abstract::Initiation of DNA synthesis by recombinant colony-stimulating factors (CSFs) was assessed in normal human marrow blast cells isolated by expression of CD34 antigen (tritiated thymidine incorporation). Continuous exposure to CSF was required. A mild increase in DNA synthesis was initiated by granulocyte CSF (G-CSF; gre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, C...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
abstract:OBJECTIVE:To investigate whether Flk1(+)CD31(-)CD34(-) cells isolated from fetal bone marrow (BM) have characteristics of hemangioblasts, i.e., progenitors of endothelial and hematopoietic cells. MATERIALS AND METHODS:Mononuclear cells from fetal BM were negatively sorted by CD45, GlyA, and CD34 micromagnetic beads, t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00087-0
更新日期:2003-07-01 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