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Quantitative cell-cycle progression analysis of the first three successive
cell cycles of granulocyte colony-stimulating factor and/or
granulocyte-macrophage colony-stimulating factor-stimulated human CD34+
bone marrow cells in relation to their colony formation
F Lardon, DR Van Bockstaele, HW Snoeck and ME Peetermans
Laboratory of Experimental Hematology, University of Antwerp (UIA/UZA),
Belgium.
The bromodeoxyuridine (BrdU)-Hoechst flow cytometric technique was applied
to study the immediate cell kinetic response of highly purified human (h)
bone marrow progenitor cells (CD(34+)-sorted fraction) to h granulocyte
colony-stimulating factor (G-CSF) and/or h granulocyte- macrophage
colony-stimulating factor (GM-CSF). The technique permits us to
differentiate cycling from noncycling cells and to make a quantitative
assessment of cell cycles after stimulation. Semisolid agar and single-cell
liquid cultures were also performed to compare these initial events to the
effects observed after 14 days of culture. The combination of G-CSF plus
GM-CSF, acting synergistically in day 14 cultures, was found to have a
subadditive effect in the first cell cycles, thereby indicating partial
overlap of the different target cells. However, this combination
accelerated transit through the cell cycle, as could be seen from the
higher number of cells in the third cell cycle after 72 hours of
stimulation. We conclude that, apart from the unresponsive cells, the CD34+
compartment consists of cells responsive to both G-CSF and GM-CSF, and
cells responsive to either one of the CSFs alone, and that the combination
of the two CSFs speeds up the cell cycle traverse rate for a significant
fraction of the target cells that are initially responsive for both G-CSF
and GM-CSF. The latter supports the hypothesis of an overlapping signalling
pathway of G-CSF and GM-CSF.
Volume 81,
Issue 12,
pp. 3211-3216,
06/15/1993
Copyright © 1993 by The American Society of Hematology

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