REGULATION OF MYELOPOIESIS BY MURINE FIBROBLASTIC AND ADIPOGENIC CELL-LINES

The regulation of hematopoiesis has been suggested to take place in cl ose association with various cell types found in the bone marrow (BM) microenvironment. In the present study the role of fibroblasts, adipoc ytes and cell surface heparan sulfate in regulating hematopoiesis in a n in vitro mouse system was examined. Mouse BM cells were allowed to a dhere to a mouse embryo fibroblast cell line (C3H 10T1/2) or a clonall y derived adipogenically determined derivative (Clone D) of the 10T1/2 cell line. Nonadherent cells were removed, cultures were overlaid wit h semisolid media supplemented with growth factors and colony formatio n by granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and multipoten tial (CFU-GEMM) progenitor cells was quantitated. Adherence and co-cul ture of BM cells with the fibroblast cell line resulted in increased n umbers of total CFU-GM and CFU-GEMM colonies. In contrast, adherence a nd co-culture of BM cells with the adipocytic cell line resulted in an increase only in CFU-GEMM colonies. Morphological analysis revealed a preferential adherence/growth of granulocyte and macrophage progenito rs at the expense of bipotent granulocyte-macrophage progenitors to th e fibroblastic cell Line and an increase in the adherence/growth of gr anulocyte progenitors to the adipogenic cell line. Progenitor cell adh erence was abolished when the fibroblastic or adipocytic cell lines we re pretreated with heparitinase. These results demonstrate enhanced pr oliferation/differentiation of hematopoietic progenitor cells when the re is direct contact between hematopoietic progenitors and cell types characteristic of those found in the microenvironment and that heparan sulfate and different types of stromal cells appear to play different roles in this interaction.