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Effects of hematopoietic growth factors on the survival of primitive stem
cells in liquid suspension culture
DM Bodine, PS Crosier and SC Clark
Clinical Hematology Branch, NHLBI, National Institutes of Health Bethesda,
MD 20892.
We have examined the effects of 10 different growth factors either alone or
in combination on colony-forming unit-spleen (CFU-S) and repopulating stem
cell survival in vitro. Either interleukin-3 (IL-3),
granulocyte-colony-stimulating factor (G-CSF), or IL-4 alone support CFU-S
in vitro. The effects of IL-3 or G-CSF could be neutralized by adding
antibodies against IL-3 or G-CSF, respectively. However, the effects of
IL-4 could be neutralized with antibodies to IL-4 as well as with
antibodies to IL-3 and G-CSF. The combinations of IL-3 and IL-6, IL-3 and
G-CSF, IL-3 and IL-1 alpha, IL-3 and granulocyte-macrophage CSF (GM-CSF),
and IL-4 and IL-6 acted synergistically to increase CFU-S number. Addition
of macrophage inflammatory protein-1 alpha (MIP-1 alpha) to IL-3 and IL-6
inhibited the increase in CFU-S number. Repopulating stem cell function was
measured in a competitive repopulation assay. Either IL-3 or IL-4 alone
could preserve stem cell function in vitro. The combinations of IL-3 and
IL-6, and IL-3 and G- CSF increased stem cell function approximately
twofold. The combinations of IL-3 + G-CSF + IL-6, and IL-4 and IL-6 (both
of which increased CFU-S number fivefold to 10-fold) decreased stem cell
function approximately fourfold. These results demonstrate that certain
combinations of growth factors can increase CFU-S number at the expense of
stem cell function.
Volume 78,
Issue 4,
pp. 914-920,
08/15/1991
Copyright © 1991 by The American Society of Hematology
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