Granulopoietic effects of human bone marrow fibroblastic cells and
abnormalities in the "granulopoietic microenvironment"
BR Greenberg, FZD Wilson and L Woo
The in vitro granulopoietic effects of adherent bone marrow fibroblastic
cells (FC) were studied in normal humans and in patients with acute
myelogenous leukemia (AML) and myeloproliferative disorders (MPD). To
determine their influence on granulopoiesis, we established FC in
liquid-phase cultures, overlaid the adherent FC with normal bone marrow
cells in agar, and subsequently measured the growth of CFU-C. When using
target marrows containing few spontaneous colonies, increased numbers of
CFU-C were found above the FC obtained from normals. No growth greater than
controls was observed in those areas lacking FC. If target marrows
contained large numbers of spontaneous CFU-C, actual inhibition of colony
formation was produced by FC co- incubation. In contrast to normals, FC
obtained from untreated AML and MPD patients typically failed to enhance
granulopoiesis. Regardless of source, FC were not synergistic with the
effects of placenta- conditioned media (typically being inhibitory) for
colony number, but were synergistic for colony size. Conditioned media
obtained from FC cultures did not enhance colony formation and actually
inhibited spontaneous colony formation. Thus, microenvironmental
abnormalities in interactions between "stromal cells" and hematopoietic
progenitors may be important in the pathogenesis and clinical expression of
hematopoietic malignancies in humans.
Volume 58,
Issue 3,
pp. 557-564,
09/01/1981
Copyright © 1981 by The American Society of Hematology
