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Combinations of recombinant colony-stimulating factors are required for
optimal hematopoietic differentiation in serum-deprived culture
CA Sieff, SC Ekern, DG Nathan and JW Anderson
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA 02115.
Previous in vitro investigations on enriched human hematopoietic
progenitors have led to the conclusion that the purified recombinant
multipoietins, interleukin 3 (IL-3) and granulocyte-macrophage colony-
stimulating factor (GM-CSF) can alone induce the formation of colonies from
a variety of multipotent and lineage committed progenitors. Since fetal
calf serum was included in these cultures and itself might contain growth
factors or other cofactors, we re-examined the actions of the CSFs in
serum-deprived conditions. Results show that both the multipoietins are
inadequate stimuli of colony formation. At maximal concentrations IL-3
alone induces only 25% of the granulocyte and macrophage colony-forming
units (CFU-G and CFU-M) produced by a T-cell conditioned medium that
contains a mixture of CSFs. When IL-3 was added at the initiation of the
cultures and erythropoietin (ep), G-CSF, or M- CSF added on day 3, almost
full recovery of erythroid, granulocytic, and monocytic colonies,
respectively, was obtained. Similar results were obtained with GM-CSF
except that fewer erythroid colonies were recovered at high concentrations,
and almost maximal CFU-M proliferation could be induced. These results show
that in serum- deprived conditions, the multipoietins must be combined with
lineage specific CSFs for full progenitor expression.
Volume 73,
Issue 3,
pp. 688-693,
02/15/1989
Copyright © 1989 by The American Society of Hematology
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