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Basic fibroblast growth factor mediates its effects on committed myeloid
progenitors by direct action and has no effect on hematopoietic stem cells
AC Berardi, A Wang, J Abraham and DT Scadden
Division of Hematology/Oncology, New England Deaconess Hospital, Harvard
Medical School, Boston, MA 02215, USA.
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.
Volume 86,
Issue 6,
pp. 2123-2129,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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