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Role of c-kit ligand in the expansion of human hematopoietic progenitor
cells
J Brandt, RA Briddell, EF Srour, TB Leemhuis and R Hoffman
Division of Hematology/Oncology, Indiana University School of Medicine,
Indianapolis.
To test the hypothesis that the c-kit ligand plays an important role in the
regulation of early events occurring during human hematopoiesis, we
determined the effect of a recombinant form of c-kit ligand, termed mast
cell growth factor (MGF), on the high-proliferative potential
colony-forming cell (HPP-CFC) and the cell responsible for initiating
long-term hematopoiesis in vitro (LTBMIC). MGF alone did not promote
HPP-CFC colony formation by CD34+ DR- CD15- marrow cells, but
synergistically augmented the ability of a combination of granulocyte-
monocyte colony-stimulating factor (GM-CSF) interleukin (IL)-3 and a
recombinant GM-CSF/IL-3 fusion protein (FP) to promote the formation of
HPP-CFC-derived colonies. MGF had a similarly profound effect on in vitro
long-term hematopoiesis. Repeated additions of IL-3, GM-CSF, or FP alone to
CD34+ DR- CD15- marrow cells in a stromal cell-free culture system
increased cell numbers 10(3)-fold by day 56 of long-term bone marrow
culture (LTBMC), while combinations of MGF with IL-3 or FP yielded 10(4)-
and 10(5)-fold expansion of cell numbers. Expansion of the number of
assayable colony-forming unit-granulocyte-monocyte (CFU- GM) generated
during LTBMC was also markedly enhanced when MGF was added in combination
with IL-3 or FP. In addition, MGF, IL-3, and FP individually led to a
twofold to threefold increase in HPP-CFC numbers after 14 to 21 days of
LTBMC. Furthermore, the effects of these cytokines on HPP-CFC expansion
during LTBMC were additive. Throughout the LTBMC, cells receiving MGF
possessed a higher cloning efficiency than those receiving IL-3, GM-CSF, or
FP alone. These data indicate that the c-kit ligand synergistically
interacts with a number of cytokines to directly augment the proliferative
capacity of primitive human hematopoietic progenitor cells.
Volume 79,
Issue 3,
pp. 634-641,
02/01/1992
Copyright © 1992 by The American Society of Hematology
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