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Stem cell factor induction of in vitro murine hematopoietic colony
formation by "subliminal" cytokine combinations: the role of "anchor
factors"
PA Lowry, D Deacon, P Whitefield, HE McGrath and PJ Quesenberry
Department of Internal Medicine, University of Virginia Health Sciences
Center, Charlottesville 22908.
The high levels of hematopoietic growth factors required for in vitro and
in vivo activity raise questions as to their role in normal hematopoietic
maintenance. We hypothesize that the use of combinations of cytokines to
stimulate hematopoietic progenitors might allow individual factors to exert
their influence at lower, more physiologically relevant concentrations.
Growth factor combinations were assessed by their ability to stimulate both
total colonies and high proliferative potential colony-forming cells
(HPP-CFC), an early murine hematopoietic progenitor, in double-layer agar
cultures. Very- low-level combinations of colony-stimulating factor
(CSF)-1, granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF),
interleukin (IL)-1 alpha, and IL-3 had little or no clonogenic capacity.
Plateau levels of rr stem cell factor (rrSCF), a c-kit ligand, used alone
also had negligible clonogenic capacity, but when combined with the
low-level combination of the other five factors produced total colony and
HPP-CFC growth approaching that produced by all factors at plateau levels.
Delayed addition experiments suggest that this effect may represent
sequential activity of SCF and the other factors. We propose a model of the
normal hematopoietic microenvironment in which SCF at locally high
concentration on the stromal cell surface "anchors" the hematopoietic stem
cell's response to multiple other cytokines at physiologically relevant
levels.
Volume 80,
Issue 3,
pp. 663-669,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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