Abstract:
OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected with a retroviral vector containing the murine IL-2 gene and transplanted into lethally irradiated syngeneic hosts. RESULTS:Productive insertion of the IL-2 gene could be demonstrated at various intervals post-transplant without impairment of hematopoietic engraftment. Endogenously augmented IL-2 release resulted in a selective increase in CD4(+), CD8(+), and NK1.1(+) population in spleen and bone marrow, as well as significant cytolytic activity against syngeneic leukemia cells in vitro. Our results also illustrate the interdependence among the magnitude of systemic IL-2 levels, the number of IL-2-transduced cells in the transplant inoculum, and the appearance of systemic toxicity. Infusion of marrow transduced with high-titer, high-expressing IL-2 retrovirus resulted in significant morbidity and mortality in the recipients. Our studies demonstrate that mortality was secondary to severe lymphocytic infiltration of liver and lung, which was associated with increased expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1. Reducing the number of IL-2-transduced cells in the bone marrow inoculum, however, resulted in significantly improved survival with no adverse events being evident during the post-transplant period. CONCLUSION:Delivery of IL-2 to the bone marrow can be achieved by transplantation of genetically modified hematopoietic cells, however, the overall feasibility is strongly influenced by the number of transduced cells in the bone marrow inocolum and/or the expression pattern of IL-2 in vivo.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kühr T,Bechter O,Dirnhofer S,Geley S,Gächter A,Pall G,Url M,Dietrich H,Oberaigner P,Klima G,Eisterer W,Hilbe W,Lukas P,Thaler Jdoi
10.1016/s0301-472x(00)00487-2keywords:
subject
Has Abstractpub_date
2000-08-01 00:00:00pages
895-906issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(00)00487-2journal_volume
28pub_type
杂志文章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::Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therap...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.10.001
更新日期:2019-11-01 00:00:00
abstract::To investigate the effect of interferon on the proliferation of normal erythroid precursor cells, various interferon preparations were added to mouse fetal liver cells cultured in a liquid microculture system. The effect of interferon was studied using cellular tritiated thymidine incorporation both in the presence an...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract:OBJECTIVE:Regulation of the cell cycle by cyclin-dependent kinase (CDK) activity occurs at multiple levels and is often altered in human cancers. Therefore, CDK activity has been targeted for drug discovery, and a number of small molecules have now been identified as CDK inhibitors. Plant cytokinin analogues with CDK i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00894-9
更新日期:2002-10-01 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::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
abstract::The circadian and circannual rhythms of committed stem cells (CFUc) were investigated by using the agar colony technique. There was a marked circadian rhythmicity, with variations between maximum and minimum colony yields of 2-5.5 times; such variations could also be seen throughout the year. A phase shift was observe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::The reproducibility and utility of an in vitro bioassay for erythropoietin were evaluated, and modifications, including the use of frozen target cells, were made. The assay, based on 3H-thymidine incorporation into phenylhydrazine-treated mouse spleen cells, showed a dose-response curve from 0.2 to 20 mU of sheep plas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract:OBJECTIVE:Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.06.007
更新日期:2008-11-01 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::Serial clonogenicity studies employing an agar CFUc culture assay are being performed on cells from CML patients to determine if clonal growth, 3HTdR suicide indices (SI) and in vitro busulfan sensitivity are of prognostic significance in predicting blastic transformation. Initial studies performed on specimens obtain...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract:OBJECTIVE:Adenoviral vectors (Ad) were widely used in gene therapy and study of gene function, but the commonly used serotype 5 adenovirus-based vectors (Ad5) could poorly transduce hematopoietic cells because of low expression of viral receptors on these cells. To overcome this limitation, we developed a retargeting a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.005
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVE:Adult T-cell leukemia (ATL) is a mature CD4(+) T-cell malignancy caused by infection with human T-lymphotrophic virus type-1 and is associated with a marked hypercalcemia in many patients. Recently, it has been proposed that macrophage inflammatory protein-1alpha (MIP-1alpha) is the clinical hallmark of hyper...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.11.013
更新日期:2008-04-01 00:00:00
abstract::Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.004
更新日期:2016-05-01 00:00:00
abstract::The concept that mesenchymal stromal cells (MSCs), a component of the hematopoietic microenvironment, can be a target for alloreactive effector cells in the context of graft-vs-host disease has not been investigated in detail. Mixed lymphocyte reaction (MLR) supernatant was used to mimic the inflammatory milieu induce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.07.011
更新日期:2012-11-01 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: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:OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.001
更新日期:2010-11-01 00:00:00
abstract::Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes origi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.07.005
更新日期:2019-08-01 00:00:00
abstract::Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.08.007
更新日期:2020-10-01 00:00:00
abstract::Several studies suggest that serum factors (thrombopoietins) regulate thrombopoiesis by altering the number, size, ploidy, and maturation rate of megakaryocytes (MK). Various in vivo systems have been used to quantitate these events. In this study, an in vitro system was developed to monitor terminal cytoplasmic matur...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-11-01 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:Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.004
更新日期:2010-11-01 00:00:00
abstract:OBJECTIVE:Myeloid ectropic viral integration site 1 (MEIS1) is a Hox cofactor known for its role in development and is strongly linked to normal and leukemic hematopoiesis. Although previous studies have focused on identifying protein partners of MEIS1 and its transcriptionally regulated targets, little is known about ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.06.006
更新日期:2010-09-01 00:00:00
abstract::Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2010.03.015
更新日期:2010-07-01 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::To investigate the value of genetic mutations in the pathogenesis and differential diagnosis of hemophagocytic lymphohistiocytosis (HLH), mutations related to blood and immune deficiency genes were analyzed in patients with HLH. Peripheral blood samples from 33 children diagnosed with HLH on the basis of the 2004 diag...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.09.024
更新日期:2019-10-01 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::We have studied the in vivo spleen colony-forming ability and marrow repopulating ability of murine bone marrow cells differing in mitochondrial activity. Following centrifugal elutriation the cells were sorted on the basis of rhodamine-123 fluorescence intensity within a predetermined light scatter window. It is show...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 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