Stem Cells, Vol 11, 319-325, Copyright © 1993 by AlphaMed Press
On control of the hematopoietic cell proliferation
E Necas, L Sefc and V Znojil
Department of Pathophysiology, First Medical Faculty, Charles University, Prague, Czech Republic.
Hematopoietic cells, detected as spleen colony forming units (CFU-S), vary
in their proliferation rate, and this can be investigated in vivo by
determining the fraction of CFU-S synthesizing DNA. A large number of
measurements of CFU-S number and the fraction synthesizing DNA has been
obtained under standardized conditions in normal mice and after a single
dose of arabinosyl cytosine (ara-C). These data are analyzed with respect
to the correlation between the number of CFU-S and their DNA-synthesizing
fraction since, in the past, it has been maintained that the CFU-S
proliferation rate responds sensitively to changes in CFU-S numbers. The
present analysis does not support this traditional view--it instead
demonstrates that natural variations in CFU-S numbers occurring in the same
range as those following ara-C do not trigger CFU- S proliferation. On the
other hand, administration of ara-C triggers most of the surviving CFU-S
into the cell cycle, while decreasing CFU-S numbers by only about 40%. Data
are also presented showing changes of CFU-S numbers and their
DNA-synthesizing fraction in mice given a single dose of cyclophosphamide
(CY). CY reduces CFU-S numbers, but the fraction synthesizing DNA can be
either increased or decreased depending on time after treatment. Both these
experimental situations argue against a close relationship between CFU-S
numbers and their proliferation rate and suggest a different or a more
complex regulation.
