International Journal of Cell Cloning, Vol 4, 357-367, Copyright © 1986 by AlphaMed Press
Granulopoiesis in long-term culture by marrow from mice with busulfan- induced chronic latent aplasia
RL Boyd, J Caro, KG Halka and AJ Erslev
Mice given high-dose busulfan therapy develop a chronic latent marrow
aplasia characterized by normal peripheral blood neutrophil numbers,
hematocrits and marrow cellularity but reduced numbers of pluripotent
hemopoietic stem cells (CFU-s) and granulocyte-monocyte progenitor cells
(CFU-gm). To study the pathogenesis of this lesion, bone marrow was
propagated in long-term marrow cultures (LTMC). Small amounts of normal
marrow readily established and sustained long-term granulopoiesis in vitro.
In contrast, inocula of marrow from busulfan- treated animals containing
three to five times as many stem and progenitor cells failed to establish
long-term granulopoiesis in vitro. These results suggest that high-dose
busulfan therapy produces a qualitative defect in either the hemopoietic
stem cells, the stromal- forming elements, or both, rendering them
incapable of establishing long-term granulopoiesis in vitro. Furthermore,
mixing experiments employing normal and busulfan-damaged marrow demonstrate
that this qualitative defect is not due to the emergence of a suppressor
cell population. LTMC can show types of marrow damage not detectable by
other techniques currently available and represent a powerful tool for
studying latent bone marrow failure.
