1,720,982 research outputs found
New insights into the characterization and ex vivo manipulation of CD34+ cells
No full textBackground and Objective. The CD34 antigen represents to date the only molecule whose expression is restricted to a small population of primitive hematopoietic progenitor cells. In the last few years,a great progress in the characterization, enumeration, and ex-vivo expansion of CD34+ cells was made. To address these issues, the Italian Society of' Experimental Hematoogy organized a Meeting in Florence on February 26, 1998.
Inf'ormation Sources. The material examined in the present reyiew includes full papers and abstracts published in journals covered by the Science Citation lndex and Medline. All the participants to the Meeting in Florence have been actively working in the field of biology and clinical application of CD34- cells. Summaries of their oral presentation at the norence Meeting are reported in the Appendix to this paper.
State of Art and Perspectives. Bone marrow, mobilized peripheral blood and cord blood are the commonly used sources ot hematopoietic cells tor transplant. Recently some guidelines for the flow cytometry enumeration of CD34+ cells were proposed by the European Yorking Group on Clinical Cell Analysis, and we herewith summarize them as follows : 1) single platform assay (absolute count and CD34* cell estimation on a single instrument, i.e. flow cytometer); 2) whole blood staining, NH4CI based erythrocyte lysis, no fixation, no washing; 3) class II or III conjugated CD34 McAbs (class II CD34 McAbs only with phycoerythrin); 4) counterstaining with CD45 McAb; 5) use of a nucleic acid dye to select viable nucleated cells; 6) acquisition of list mode data containing at least 50-100 CD34• cells during data acquisition; 7) sequential gating strategy during list mode data analysis. As far as the ex vivo expansion of cord blood stem cells is concerned, it can be stated that this technique could mafte the use of cord blood transplant feasible also for adult patients. Recently we developed a stroma-free culture system in which a progressive, increasingly greater production of hemopoietic progenitors belonging to all the hematopoietic lineages was sustained for over six months. A similar sustained and prolonged expansion of the most primitive stem cells that can be detected in vitro (LTC-IC), was also documented. The extremely prolonged maintenance and the massive expansions suggest that extensive self-renewal and little differentiation can be triggered in vitro by FLT3/FLK2 ligand (FL) plur c-mpl ligand (throm- bopoietin) and this could represent a first step towards the implementation of clinical expansion- transplantation strategies
Cell therapy: filling the gap between basic science and clinical trials October 15-17, 2001, Rome, Italy.
No full textEffect of acidic and basic isoferritins on in vitro growth of human granulocyte-monocyte progenitors
No full textAcidic isoferritins have been previously found to be highly potent inhibitors of hematopoietic progenitors at concentrations of 10(-16) to 10(-18) mol/L, and it has been suggested that acidic isoferritin inhibitory activity plays a role in the regulation of normal hematopoiesis and also in the pathogenesis of leukemia. To characterize the ferritin species that affect the in vitro growth of human colony-forming unit-granulocyte-macrophage (CFU-GM), we tested different preparations of basic (L-subunit-rich) and acidic (H-subunit-rich) isoferritins. Three preparations of human liver (basic) ferritin did not show any effects on CFU-GM growth at concentrations up to 10(-9) mol/L, irrespective of the degree of glycosylation. Acidic isoferritins were purified both from HeLa cells and human heart. HeLa cell ferritin did not affect in vitro colony formation. One of two preparations of human heart ferritin, containing 5% glycosylated ferritin, showed a mean inhibition of 26% +/- 8% of the control at 10(-9) mol/L (P less than .02), whereas the other preparation, which contained no glycosylated ferritin, did not show any effect of CFU-GM growth. A preparation enriched for glycosylated acidic isoferritins from human heart was found to produce a mean inhibition of 32% +/- 11% of the control at 10(-9) mol/L (P less than .01), whereas another one was ineffective. A significant part of the inhibitory activity was removed by preincubation with the monoclonal antibody 2A4 directed against human heart ferritin. The present findings indicate that basic isoferritins, ie, the predominant ferritin type in human blood, have no effect on the growth of human CFU-GM, and this is in keeping with indirect clinical evidence. Inhibition of colony formation may be obtained by some preparations of acidic isoferritins that are rich in H subunits and bind to concanavalin A. The mechanism(s) responsible for this are not clear, but the effective concentrations are higher than those found in human blood both under normal conditions and in leukemia. At present, the physiologic significance of the observed inhibitory activity is uncertain
Evaluation of expression and phosphorylation status of SHC adaptor proteins and ERK-JNK MAP kinases in ex vivo expanded hematopoietic stem cells
No full textHigh self-renewal of human primitive hematopoietic stem cells taken from cord blood is uncoupled from sustained ERK activity
No full textCytokine induced killer cells as adoptive immunotherapy strategy to augment graft versus tumor after hematopoietic cell transplantation
No full textDonor lymphocyte infusion (DLI) is used to increase the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplant (HCT). The limited spectrum of activity and high risk of graft versus host disease (GVHD) remain major limitations of this approach. The finding of new cell populations for adoptive immunotherapy, with the ability to separate GVT from GVHD, would be useful. Here we review the main basic, preclinical and clinical research on cytokine-induced killer (CIK) cells, highlighting the aspects of their antitumor and alloreactive potentials that might favourably affect the balance between GVT and GVHD. CIK cells are ex vivo-expanded T lymphocytes sharing NK markers and endowed with a potent MHC-unrestricted antitumor activity against haematological and solid malignancies. Studies in preclinical animal models have demonstrated their low GVHD potential when infused across MHC-barriers, and recent clinical studies seem to confirm these findings in patients with hematological malignances relapsing after HCT. If consolidated with larger clinical trials, adoptive immunotherapy with CIK cells might represent an effective alternative to classic DLI, helping HCT to succesfully meet current challenges like the extension across major HLA-barriers and application to solid tumors. © 2009 Informa UK Ltd. All rights reserved
Attività della proteina del segnale ERK nell'auto-mantenimento, proliferazione e differenziazione delle cellule staminali ematopoietiche umane pluripotenti
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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