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Interrelationship between mitosis and endomitosis in cultures of human
megakaryocyte progenitor cells [published erratum appears in Blood 1987
May;69(5):1547]
M Arriaga, K South, JL Cohen and EM Mazur
Sera from dogs rendered aplastic by total-body irradiation stimulate human
bone marrow megakaryocyte progenitors to form megakaryocyte colonies in
plasma clot cultures. In this investigation, we evaluated the effects of
varying concentrations of such sera on both the mitotic and endomitotic
phases of human megakaryocyte development in vitro. When low concentrations
of aplastic canine sera (2.5% to 5.0% [vol/vol]) were added to cultures of
human peripheral blood mononuclear cells in place of normal AB serum,
megakaryocyte colony formation was augmented fivefold, cell numbers per
colony increased approximately 2.5- fold, and the geometric mean
megakaryocyte ploidy almost doubled. Further increasing the aplastic canine
serum concentration from 10% to 30% (vol/vol) stimulated no additional
colony formation. However, there was a further augmentation of cell numbers
per colony associated with a progressive decrease in the mean megakaryocyte
ploidy. Megakaryocyte cultures were harvested after 7, 12, 15, and 19 days
of incubation, and these demonstrated that the lower mean ploidy values
found at the higher concentrations of aplastic canine serum did not result
from delayed endoreduplication. At all aplastic serum concentrations
evaluated, there existed a strong correlation between nuclear ploidy and
cell diameter. We conclude that both the mitotic and endomitotic events in
human megakaryocytopoiesis may be influenced by a factor or factors present
in aplastic canine serum. At lower in vitro concentrations, such sera
stimulate both mitosis and endomitosis, which promotes the development of
megakaryocyte colonies composed of larger cells with a higher mean ploidy.
With increasing aplastic serum concentrations, colony formation plateaus
and mitosis is favored over endomitosis. This results in colonies composed
of more numerous but smaller megakaryocytes with a lower mean ploidy. Our
data suggest that the size and extent of polyploidization that can be
achieved by a developing megakaryocyte may be influenced by the mitotic
prior history of its immediate precursor cell.
Volume 69,
Issue 2,
pp. 486-492,
02/01/1987
Copyright © 1987 by The American Society of Hematology
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