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FLT3/FLK2 ligand promotes the growth of murine stem cells and the expansion
of colony-forming cells and spleen colony-forming units
S Hudak, B Hunte, J Culpepper, S Menon, C Hannum, L Thompson-Snipes and D Rennick
Department of Immunology, DNAX Research Institute of Molecular and Cellular
Biology, Palo Alto, CA 94304, USA.
The effect of FLT3/FLK2 ligand (FL) on the growth of primitive
hematopoietic cells was investigated using ThyloSca1+ stem cells. FL was
observed to interact with a variety of factors to initiate colony formation
by stem cells. When stem cells were stimulated in liquid culture with FL
plus interleukin (IL)-3, IL-6, granulocyte colony- stimulating factor
(G-CSF), or stem cell factor (SCF), cells capable of forming colonies in
secondary methylcellulose cultures (CFU-c) were produced in high numbers.
However, only FL plus IL-6 supported an increase in the number of cells
capable of forming colonies in the spleens of irradiated mice (CFU-s).
Experiments with accessory cell- depleted bone marrow (Lin- BM) showed that
FL alone lacks significant colony-stimulating activity for progenitor
cells. Nevertheless, FL enhanced the growth of granulocyte-macrophage
progenitors (CFU-GM) in cultures containing SCF, G-CSF, IL-6, or IL-11. In
these assays, FL increased the number of CFU-GM initiating colony formation
(recruitment), as well as the number of cells per colony (synergy). Many of
the colonies were macroscopic and contained greater than 2 x 10(4)
granulocytes and macrophages. Therefore, FL appears to function as a potent
costimulus for primitive cells of high proliferative potential (HPP). FL
was also observed to costimulate the expansion of CFU-GM in liquid cultures
of Lin- BM. In contrast, FL had no growth- promoting affects on progenitors
committed to the erythrocyte, megakaryocyte, eosinophil, or mast cell
lineages.
Volume 85,
Issue 10,
pp. 2747-2755,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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