The regulation of hemopoiesis in long-term bone marrow cultures. II.
Stimulation and inhibition of stem cell proliferation
D Toksoz, TM Dexter, BI Lord, EG Wright and LG Lajtha
The isolation of a DNA synthesis inhibitor (NBME fraction IV) and
stimulator (RBME fraction III) specific for the hemopoietic stem cell
(CFU-s) from freshly isolated normal adult and regenerating murine bone
marrow, respectively, has been well documented. We have utilized long- term
liquid bone marrow cultures in a further analysis of the role of these
factors in the regulation of CFU-s proliferation. Our results show that
shortly after feeding, at a time when the cultured CFU-s are actively
proliferating, high levels of the hemopoietic stem cell proliferation
stimulator fraction III can be isolated from the culture medium. In
contrast, the presence of essentially noncycling CFU-s found in cultures
fed 8-10 days previously correlates with high levels of the hemopoietic
stem cell inhibitor fraction IV. These results suggest that a certain
balance between these factors determines CFU-s proliferation in the
long-term cultures. In support of this, DNA synthesis in actively cycling
CFU-s in the long-term cultures is inhibited for at least 3 days by the
addition of excess NBME fraction IV (inhibitor). Furthermore, DNA synthesis
in noncycling cultured CFU-s is stimulated for at least 5 days by the
addition of RBME fraction III (stimulator).
Volume 55,
Issue 6,
pp. 931-936,
06/01/1980
Copyright © 1980 by The American Society of Hematology
