Granulopoietic effects of human bone marrow fibroblastic cells and abnormalities in the "granulopoietic microenvironment"

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.