scholarly journals Basic fibroblast growth factor mediates its effects on committed myeloid progenitors by direct action and has no effect on hematopoietic stem cells

Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2123-2129 ◽  
Author(s):  
AC Berardi ◽  
A Wang ◽  
J Abraham ◽  
DT Scadden
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Fibroblast Growth Factor ◽  
Colony Formation ◽  
Fibroblast Growth ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Myeloid Progenitor ◽  
Stimulating Factor

Basic fibroblast growth factor or fibroblast growth factor-2 (FGF) has been shown to affect myeloid cell proliferation and hypothesized to stimulate primitive hematopoietic cells. We sought to evaluate the effect of FGF on hematopoietic stem cells and to determine if FGF mediated its effects on progenitor cells directly or through the induction of other cytokines. To address the direct effects of FGF, we investigated whether FGF induced production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, IL-6, granulocyte colony- stimulating factor, or granulocyte-macrophage colony-stimulating factor by two types of accessory cells, bone marrow (BM) fibroblasts and macrophages. We further evaluated whether antibodies to FGF-induced cytokines affected colony formation. To determine if FGF was capable of stimulating multipotent progenitors, we assessed the output of different colony types after stimulation of BM mononuclear cells (BMMC) or CD34+ BMMC and compared the effects of FGF with the stem cell active cytokine, kit ligand (KL). In addition, a subset of CD34+ BMMC with characteristics of hematopoietic stem cells was isolated by functional selection and their response to FGF was evaluated using proliferation, colony-forming, and single-cell polymerase chain reaction (PCR) assays. We determined that FGF had a stimulatory effect on the production of a single cytokine, IL-6, but that the effects of FGF on colony formation were not attributable to that induction. FGF was more restricted in its in vitro effects on BM progenitors than KL was, having no effect on erythroid colony formation. FGF did not stimulate stem cells and FGF receptors were not detected on stem cells as evaluated by single-cell reverse transcription PCR. In contrast, FGF receptor gene expression was detected in myeloid progenitor populations. These data support a directly mediated effect for FGF that appears to be restricted to lineage-committed myeloid progenitor cells. FGF does not appear to modulate the human hematopoietic stem cell.

scholarly journals Inhibition of day-12 spleen colony-forming units by a monoclonal antibody to the murine macrophage/monocyte colony-stimulating factor receptor

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2731-2734 ◽  
Author(s):  
GL Gilmore ◽  
RK Shadduck
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Growth Factor Receptor ◽  
Hematopoietic Growth Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Colony Forming Units ◽  
Stimulating Factor ◽  
Specific Control

Primitive hematopoietic stem cells differentiate into committed progenitors that are thought to selectively express hematopoietic growth factor receptor(s), thereby acquiring hematopoietic growth factor responsiveness. To assess whether hematopoietic stem cells express hematopoietic growth factor receptors, the progenitor activity of bone marrow (BM) fractions, isolated by expression of receptors for macrophage/monocyte colony-stimulating factor (M-CSF), were examined. Recovery of day-12 spleen colony-forming units (CFU-S) is diminished in both M-CSF receptor-positive (M-CSFR+) and M-CSFR-fractions, indicating antibody inhibition of day-12 CFU-S. Incubation of BM cells with antibody without fractionation inhibits 50% to 60% of day-12 CFU-S. This inhibition is specific (control antibodies have no effect) and reversible by removal of bound antibody at low pH. Incubating BM cells with control or antireceptor antibody does not affect day-8 CFU-S, which are predominantly erythroid. Treating sublethally irradiated mice with antibody inhibits endogenous day-12 CFU-S. These results indicate that some early progenitors express M-CSFRs, and blocking M-CSFRs inhibits the ability of these progenitors to form colonies, possibly because of inactivation caused by prolonged receptor blockade.

scholarly journals Fibroblast Growth Factor-1 and -2 Preserve Long-Term Repopulating Ability of Hematopoietic Stem Cells in Serum-Free Cultures

Stem Cells ◽  
2006 ◽  
Vol 24 (6) ◽  
pp. 1564-1572 ◽  
Author(s):  
Joyce S.G. Yeoh ◽  
Ronald van Os ◽  
Ellen Weersing ◽  
Albertina Ausema ◽  
Bert Dontje ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Hematopoietic Stem ◽  
Serum Free

scholarly journals In Vitro Generation of Long-Term Repopulating Hematopoietic Stem Cells by Fibroblast Growth Factor-1

2003 ◽  
Vol 4 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Gerald de Haan ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Ronald van Os ◽  
Leonid V. Bystrykh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hematopoietic Stem Cells ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Hematopoietic Stem

Hematopoietic stem cells expanded by fibroblast growth factor-1 are excellent targets for retrovirus-mediated gene delivery

2005 ◽  
Vol 33 (12) ◽  
pp. 1459-1469 ◽  
Author(s):  
Aleksandra Crcareva ◽  
Toshiki Saito ◽  
Atsushi Kunisato ◽  
Keiki Kumano ◽  
Takahiro Suzuki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Gene Delivery ◽  
Hematopoietic Stem Cells ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Hematopoietic Stem

scholarly journals Basic fibroblast growth factor stimulates myelopoiesis in long-term human bone marrow cultures

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 954-960 ◽  
Author(s):  
EL Wilson ◽  
DB Rifkin ◽  
F Kelly ◽  
MJ Hannocks ◽  
JL Gabrilove
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Progenitor Cells ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Colony Stimulating Factor ◽  
Low Concentrations ◽  
Stimulating Factor

Abstract We previously showed that basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow (BM) stromal cells and significantly delays their senescence. In the present study, we demonstrated that low concentrations of bFGF (0.2 to 2 ng/mL) enhance myelopoiesis in long-term human BM culture. Addition of bFGF to long- term BM cultures resulted in an increase in (a) the number of nonadherent cells (sixfold), particularly those of the neutrophil granulocyte series; (b) the number of nonadherent granulocyte colony- stimulating factor (G-CSF)- and granulocyte-macrophage colony- stimulating factor (GM-CSF)-responsive progenitor cells; (c) the number of adherent foci of hematopoietic cells (10-fold); and (d) the number of progenitor cells in the adherent stromal cell layer. These effects were not noted with higher concentrations of bFGF (20 ng/mL). Thus, low concentrations of bFGF effectively augment myelopoiesis in human long- term BM cultures, and bFGF may therefore be a regulator of the hematopoietic system in vitro and in vivo.

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Abstract Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

Effect of FLT3 Ligand and Granulocyte Colony-Stimulating Factor on Expansion and Mobilization of Facilitating Cells and Hematopoietic Stem Cells in Mice: Kinetics and Repopulating Potential

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3177-3188 ◽  
Author(s):  
Michael Neipp ◽  
Tatiana Zorina ◽  
Michele A. Domenick ◽  
Beate G. Exner ◽  
Suzanne T. Ildstad
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mononuclear Cells ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Flt3 Ligand ◽  
Hematopoietic Stem ◽  
Murine Bone Marrow ◽  
Stimulating Factor

Abstract We have previously identified a cellular population in murine bone marrow that facilitates engraftment of highly purified hematopoietic stem cells (HSC) across major histocompatibility complex (MHC) barriers without causing graft-versus-host disease. Here we investigated the effect of flt3 ligand (FL) and granulocyte colony-stimulating factor (G-CSF) on the mobilization of facilitating cells (FC) and HSC into peripheral blood (PB). Mice were injected with FL alone (day 1 to 10), G-CSF alone (day 4 to 10), or both in combination. The number of FC (CD8+/βTCR−/γδTCR−) and HSC (lineage−/Sca-1+/c-kit+) was assessed daily by flow cytometry. Lethally irradiated allogeneic mice were reconstituted with PB mononuclear cells (PBMC). FL and G-CSF showed a highly significant synergy on the mobilization of FC and HSC. The peak efficiency for mobilization of FC (21-fold increase) and HSC (200-fold increase) was reached on day 10. Our data further suggest that the proliferation of FC and HSC induced by FL in addition to the mobilizing effect mediated by G-CSF might be responsible for the observed synergy of both growth factors. Finally, the engraftment potential of PBMC mobilized with FL and G-CSF or FL alone was superior to PBMC obtained from animals treated with G-CSF alone. Experiments comparing the engraftment potential of day 7 and day 10 mobilized PBMC indicate that day 10, during which both FC and HSC reached their maximum, might be the ideal time point for the collection of both populations. © 1998 by The American Society of Hematology.

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