Abstract:
OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current European and Italian Good Manufacturing Practice (eIGMP) conditions. Here, we describe in vitro and in vivo validation of the phase I/II protocol for CD34+ expansion of thawed CB units according to the current Cell Therapy Products (CTPs) Guidelines. MATERIALS AND METHODS:CB units were thawed and 25% of the total volume was processed for CD34+ selection by CliniMACS. The 75% of the unit was immediately refrozen. CD34+ cells were expanded for 3 weeks with stem cell factor, Flt-3/Flk-2 ligand, thrombopoietin, and interleukin-6. RESULTS:In vitro results demonstrated that this culture system induces expansion of thawed CD34+ (median value = 8.3). In vivo data demonstrated that after culture, the final CTPs maintain their repopulating ability in nonobese diabetic severe combined immunodeficient (SCID) mice. Limiting dilution assays performed by injecting decreasing doses of expanded CD34+ cells revealed that the frequency of SCID repopulating cells after ex vivo expansion is 1:8,034. Analyses for sterility, viability, cell senescence, and cytogenetic assessment demonstrated that expansion procedures in eIGMP conditions are safe for clinical protocols. CONCLUSIONS:This offers promising new options for expansion of allogenic HSCs and also for autologous usage in transplantation and other cell therapy protocols.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Gunetti M,Ferrero I,Rustichelli D,Berger M,Gammaitoni L,Timeus F,Piacibello W,Aglietta M,Fagioli Fdoi
10.1016/j.exphem.2007.08.030subject
Has Abstractpub_date
2008-02-01 00:00:00pages
235-43issue
2eissn
0301-472Xissn
1873-2399pii
S0301-472X(07)00556-5journal_volume
36pub_type
杂志文章,多中心研究abstract::Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVE:The mechanism for anagrelide's potent platelet lowering activity in human subjects is not well defined. Studies related to anagrelide function have been hampered by its lack of activity in nonhuman primates and water insolubility. In an effort to define the mechanism whereby anagrelide exerts its therapeutic ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00742-1
更新日期:2001-12-01 00:00:00
abstract::Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of mega...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult A...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.02.010
更新日期:2016-06-01 00:00:00
abstract::To evaluate the effects of thymocytes from anemic W/WV mice on hemopoiesis in vitro, we co-cultured thymocytes from W/WV mice or from their non-anemic +/+ littermates with W/WV or +/+ marrow cells in semi-solid systems designed to foster colonial growth from neutrophil/macrophage (CFUNM), early erythroid (BFUE), late ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::The etiology of thrombocytopenia is important in treatment and management of the condition. Most platelet parameters that are routinely analyzed in the diagnostic laboratory have not proven useful in identifying the etiology, while specialized assays suffer from poor standardization and lack of agreement between labor...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.exphem.2019.09.001
更新日期:2019-10-01 00:00:00
abstract::The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated splee...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.12.002
更新日期:2019-02-01 00:00:00
abstract::Hematopoiesis in continuous bone marrow culture is dependent upon close-range interaction between hematopoietic cells and marrow-derived adherent cells. The latter have been shown to include a significant proportion of fibroblastic elements, synthesizing the attachment protein fibronectin. The role of fibronectin in c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract:OBJECTIVE:Generation and expansion of pluripotent unrestricted somatic stem cells (USSCs) and mesenchymal cells (MSCs) from human cord blood as well their functional characterization were assessed. METHODS:USSC generation was initiated from fresh and cryopreserved cord blood (CB). Culture conditions and functional ass...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.07.011
更新日期:2006-11-01 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::Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synth...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00054-x
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 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::Regeneration of the bone marrow microenvironment after transplantation of allogeneic hematopoietic stem cells is poorly explored. The goal of our study was to investigate this process focusing on immunologic factors: concentrations of selected cytokines, expression of immunosuppressive proteins CD47 and CD274 on hemat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.08.001
更新日期:2016-12-01 00:00:00
abstract::Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::Four types of colonies can be formed by progenitor cells (CFUc) in double layer agar cultures: eosinophil, granulocyte, macrophage, and mixed granulocyte-macrophage. We have developed a method for in situ staining of intact agar plates with luxol fast blue and acetoorcein employed to differentiate the type of colonies...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. Although leukemogenesis largely results from abnormal gene...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.07.001
更新日期:2018-10-01 00:00:00
abstract::In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00747-0
更新日期:2001-12-01 00:00:00
abstract::Between 30 and 40% of the CSF present in agar was depleted after culture for 1 week with 50,000 nucleated murine bone marrow cells. No statistically significant difference could be detected between this depletion and the extent of depletion of CSF when the amount present was halved. There was no evidence that toxic or...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract:OBJECTIVE:alpha4 Integrins are major players in lymphoid cell trafficking and immune responses. However, their importance in lymphoid reconstitution and function, studied by antibody blockade or in genetic models of chimeric animals with alpha4(KO) embryonic stem (ES) cells, competitive repopulation experiments with fe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.03.008
更新日期:2008-08-01 00:00:00
abstract::We have reported modulation, by cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and by hormonal cyclic-adenosine-monophosphate (cAMP) agonists, of hematopoietic growth factor production in the murine marrow adherent cell line +/+(-)1.LDA11. Previously, we reported that increased in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 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:OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.005
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:To evaluate feasibility, safety, and efficacy of peripheral blood stem cell collection (PBSCC) and autologous stem cell transplantation (ASCT), to treat patients diagnosed of high-risk or relapsed HIV-associated lymphoma (HIV+ Ly), responding to highly active antiretroviral therapy (HAART). METHODS:Prospecti...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.exphem.2004.12.008
更新日期:2005-04-01 00:00:00
abstract::Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although ident...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.08.003
更新日期:2017-11-01 00:00:00
abstract::Thrombocytopenia is an important clinical problem for many acquired immunodeficiency syndrome (AIDS) patients. Recently, the utility of recombinant cytokines in alleviating the hematopoietic complications of AIDS and AIDS therapy has been evaluated. The newly cloned cytokine stem cell factor (SCF) has been demonstrate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract:OBJECTIVE:Cyclosporine A (CsA), known as an effective immunosuppressive agent, is widely used in clinical fields. Mesenchymal stem cells may exert immunomodulatory effects on the immune system, but the exact mechanisms underlying them remain controversial. Here we investigated whether human adipose tissue-derived mesen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.10.009
更新日期:2011-02-01 00:00:00