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Steel factor (c-kit ligand) promotes the survival of hematopoietic
stem/progenitor cells in the absence of cell division
JR Keller, M Ortiz and FW Ruscetti
Biological Carcinogenesis and Development Program, National Cancer
Institute-Frederick Cancer Research and Development Center, MD 21702- 1201,
USA.
It is known that the majority of primitive hematopoietic progenitors are in
a noncycling quiescent state. In addition, normal hematopoietic progenitors
and progenitor cell lines show an absolute dependence on growth factors for
their survival in vitro, yet the effect of growth factors on progenitor
cell survival has not been separated from effects on both proliferation and
differentiation. Using an in vitro assay system, we examined whether growth
factors could promote the survival of stem cells in culture in the absence
of cell division. These studies show that steel factor (SLF) and, to a
lesser extent, interleukin-3 (IL- 3) directly promoted the survival of
elutriated bone marrow progenitor cells (countercurrent centrifugal
elutriation [CCE]-27) that are enriched for primitive hematopoietic
progenitors that respond to the combination of SLF plus IL-3. Furthermore,
SLF promoted the survival of short-term reconstituting cells (STRC), and
long-term reconstituting cells (LTRC) with trilineage reconstitution
potential in vivo. In comparison, granulocyte colony-stimulating factor
(G-CSF), IL-6, leukemia inhibitory factor, IL-11, IL-1, granulocyte
macrophage CSF (GM- CSF), and macrophage CSF (M-CSF) had no effect on the
survival of these cells. In the presence of mitotic inhibitors (nocodazole
or aphidicolin), SLF promoted the survival of CCE-27 progenitor cells that
respond to the combination of SLF plus IL-3 in vitro and STRCs and LTRCs
that are detected in vivo. Taken together, these data show that SLF can
directly promote the survival of hematopoietic progenitor cells in the
absence of cell division.
Volume 86,
Issue 5,
pp. 1757-1764,
09/01/1995
Copyright © 1995 by The American Society of Hematology
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