Abstract：
OBJECTIVE:Recent clinical trials of adoptive immunotherapy showed diminished reactivity of human T cells upon ex vivo manipulation. For a safe and effective clinical application of human T cells, it is necessary to improve ex vivo manipulation procedures and evaluate their impact on in vivo functionality. However, there is no preclinical model for quantitative assessment of in vivo functionality of human T cells. In this study, we investigated the feasibility of using the huPBMC- RAG2(-/-)gammac(-/-) xenogeneic mouse model. As a first example, we compared 3 different ex vivo culture conditions for human T cells. METHODS:RAG2(-/-)gammac(-/-) mice received cultured human T cells that were stimulated via CD3 alone or costimulated via CD28 (CD3/28) and/or human 4-1BB (CD3/28/4-1BB). Engraftment levels and survival of the cells were measured. The dynamics of the human T cell phenotypes were analyzed during culture and in vivo, as well as the mechanism of the xenoresponse. RESULTS:Engraftment potential was improved twofold for costimulation compared to CD3 alone (p < 0.001). Phenotypic analysis showed a strikingly similar pattern of development towards CD4(+) and CD8(+) effector and effector-memory cells, suggesting antigen-driven survival and expansion. All parameters used to analyze different effects on in vivo T-cell functionality, like culture condition, engraftment levels, survival of the cells over time, or xenogeneic graft-vs-host disease were absolutely independent of the distribution of the T cell population in vivo following contact with xeno-antigen. CONCLUSION:The huPBMC-RAG2(-/-)gammac(-/-) xenogeneic transplant model is the most sensitive to date for in vivo functional evaluation of human T cells.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
van Rijn RS,Simonetti ER,Hagenbeek A,Bonyhadi M,Storm G,Martens AC,Ebeling SBdoi
10.1016/j.exphem.2006.09.018subject
Has Abstractpub_date
2007-01-01 00:00:00pages
117-27issue
1eissn
0301-472Xissn
1873-2399pii
S0301-472X(06)00640-0journal_volume
35pub_type
杂志文章abstract：:Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-05-01 00:00:00
abstract：:The Fanconi anemia group C gene (FAC) encodes a 63-kDa protein that plays a role in the growth and differentiation of hematopoietic progenitor cells and in cellular resistance to bifunctional cross-linking agents. The function of the gene product is unknown, as are the factors that govern expression of the gene itself...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Retroviral gene marking has been used successfully in preclinical and clinical transplantation settings. Highly sensitive techniques for vector insertion-site determination, such as linear amplification-mediated polymerase chain reaction (LAM-PCR) in conjunction with next-generation sequencing, have been introduced to...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.09.003
更新日期：2013-01-01 00:00:00
abstract：:The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce ther...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:The present study was undertaken to determine whether neutrophilic granulocytes leave the vascular bed and enter body tissues, particularly the lung, in pathogen-free mice under normal steady state conditions and also under inflammatory stress. Tissues from normal mice and from mice with granulocytosis-producing tumor...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results r...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.08.028
更新日期：2008-01-01 00:00:00
abstract：OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.017
更新日期：2004-11-01 00:00:00
abstract：:We compared the cell division behavior of CD34(-) and CD34(+) (CD33/CD38/CD71)-negative (Lin(-)) CD133(+) cord blood cells stimulated with the cytokines Flt3-ligand, stem cell factor, and thrombopoietin. Within a 4-day time frame, Lin(-)CD34(-) CD133(+) (CD34(-)) cells underwent more cell divisions in serum-free cultu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.05.016
更新日期：2007-09-01 00:00:00
abstract：:Embryonic and adult stem cell populations have great potential value in medicine, and hematopoietic stem cells are already being used in transplantation. Definition of these populations to increase our understanding of the programs that control differentiation, self-renewal, and possibly plasticity would be of great i...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2003.08.012
更新日期：2003-12-01 00:00:00
abstract：:Phagocytic cells are characterized by their ability to generate superoxide anions upon activation by appropriate stimuli. UM384, a myelomonocytic cell line, was shown to be defective in this oxidase activity as measured by nitroblue tetrazolium or cytochrome c reduction. Cytochrome b558, a unique pigment present in ph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00680-9
更新日期：2001-04-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Many studies have provided evidence that both genetic and environmental factors induce atherosclerosis, leading thus to cardiovascular complications. Atherosclerosis is an inflammatory disease, and aging is strongly associated with the develop...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.12.006
更新日期：2020-03-01 00:00:00
abstract：:The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity....
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：OBJECTIVE:The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the s...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.07.019
更新日期：2006-12-01 00:00:00
abstract：:An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：OBJECTIVE:Donor T cells expressing lymph node homing receptors are the foremost initiators of acute graft-vs-host disease (aGVHD), and a high proportion of CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been shown to confer a high risk of aGVHD without interfering in other outcomes. METHODS:Na...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2007.03.006
更新日期：2007-06-01 00:00:00
abstract：:Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high con...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-07-01 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：OBJECTIVE:Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this proble...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.05.026
更新日期：2004-08-01 00:00:00
abstract：:Transforming growth factor β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell function, as a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.02.001
更新日期：2016-05-01 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：OBJECTIVE:Hematopoietic stem and progenitor cells normally reside in the bone marrow but can be mobilized into the peripheral blood following treatment with granulocyte colony-stimulating factor (G-CSF) or myelosuppressive chemotherapy. Although the number of transplants performed with mobilized blood currently exceeds...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00788-9
更新日期：2002-05-01 00:00:00
abstract：:The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinity for IgG, but also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containing motifs within their cytoplasmic doma...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：OBJECTIVE:Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.01.002
更新日期：2006-04-01 00:00:00
abstract：OBJECTIVE:A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS:The HSC activity of porcine c-kit+ BMCs was ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00197-8
更新日期：2003-09-01 00:00:00
abstract：OBJECTIVE:We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.06.009
更新日期：2009-10-01 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：:We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:The anemia of Belgrade b/b rats has been shown to be due to intracellular iron deficiency. The aim of this study of erythropoiesis at the progenitor cell level in these rats was to determine if a defect is present in the early phase of red cell production. Both erythroid colony-forming unit (CFU-E)- and erythroid burs...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
