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Leukemia inhibitory factor/human interleukin for DA cells: a growth factor
that stimulates the in vitro development of multipotential human
hematopoietic progenitors
C Verfaillie and P McGlave
Department of Medicine, University of Minnesota Medical School, Minneapolis
55455.
We investigated the in vitro hematopoietic stimulatory activity of leukemia
inhibitory factor/human interleukin for DA cells (LIF/HILDA) on bone marrow
progenitor populations in 17 normal individuals. In serum-free cultures
LIF/HILDA did not induce colony growth. In serum containing media,
LIF/HILDA stimulated the growth of colony forming unit (CFU)-MIX and CFU-EO
in a dose-dependent fashion and resulted in an increased CFU-MIX and burst
forming unit-erythrocytes (BFU-E) colony size. Similar stimulatory effects
were seen on a highly purified hematopoietic progenitor population obtained
after immunomagnetic depletion of mature myeloid precursors and lymphoid
cells. Addition of LIF/HILDA to cultures containing maximally stimulatory
concentrations of recombinant human interleukin-3 (rhuIL3), rhuIL3 +
rhuIL6, or rhu granulocyte-macrophage colony-stimulating factor (rhu
GM-CSF) in serum containing media significantly increased the number of
CFU-MIX and eosinophil colonies and increased size and cluster number of
CFU-MIX and BFU-E. Depletion of accessory T lymphocytes or monocytes from
bone marrow progenitors did not alter the response of hematopoietic
precursors to LIF/HILDA. A similar increased colony growth was seen when
LIF/HILDA was added to cultures of positively selected CD34/HLA- DR+ or
CD34+/HLA-DR- bone marrow hematopoietic progenitor cells stimulated with
maximally stimulatory concentrations of rhuIL3 + rhuIL6. LIF/HILDA is a
novel cytokine capable of stimulating growth and proliferation of
multi-lineage, erythroid, and eosinophil colonies in the presence of serum.
LIF/HILDA exerts its activity by direct interaction with highly purified
immature bone marrow progenitor cells, has an additive effect when used
with other cytokines known to stimulate primitive hematopoietic precursors,
and does not require accessory cells.
Volume 77,
Issue 2,
pp. 263-270,
01/15/1991
Copyright © 1991 by The American Society of Hematology
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