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Cytokine-induced selective expansion and maturation of erythroid versus
myeloid progenitors from purified cord blood precursor cells
H Mayani, W Dragowska and PM Lansdorp
Terry Fax Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
To study the role of different cytokine combinations on the proliferation
and differentiation of highly purified primitive progenitor cells, a
serum-free liquid culture system was used in combination with phenotypic
and functional analysis of the cells produced in culture. CD34+ CD45RAlo
CD71lo cells, purified from umbilical cord blood by flow cytometry and cell
sorting, were selected for this study because of their high content of
clonogenic cells (34%), particularly multipotent progenitors (CFU-MIX, 12%
of all cells). Four cytokine combinations were tested: (1) mast cell growth
factor (MGF; a c-kit ligand) and interleukin-6 (IL-6); (2) MGF, IL-6, IL-3,
and erythropoietin (Epo); (3) MGF, IL-6, granulocyte-macrophage colony-
stimulating factor (GM-CSF)/IL-3 fusion protein (FP), macrophage colony-
stimulating factor (M-CSF), and granulocyte-CSF (G-CSF); and (4) MGF, IL-6,
FP, M-CSF, G-CSF, and Epo. Maximum numbers of erythroid progenitors (BFU-E,
up to 55-fold increase) and mature erythroid cells were observed in the
presence of MGF, IL-6, IL-3, and Epo, whereas maximum levels of myeloid
progenitors (CFU-C, up to 70-fold increase) and mature myeloid cells were
found in cultures supplemented with MGF, IL-6, FP, M-CSF, and G-CSF. When
MGF, IL-6, FP, M-CSF, G-CSF, and Epo were present, maximum levels of both
erythroid and myeloid progenitors and their progeny were observed. These
results indicate that specific cytokine combinations can act directly on
primitive hematopoietic cells resulting in significant expansion of
progenitor cell numbers and influencing their overall patterns of
proliferation and differentiation. Furthermore, the observations presented
in this study suggest that the cytokine combinations used were unable to
bias lineage commitment of multipotent progenitors, but rather had a
permissive effect on the development of lineage-restricted clonogenic
cells.
Volume 81,
Issue 12,
pp. 3252-3258,
06/15/1993
Copyright © 1993 by The American Society of Hematology

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