SUPPORT VERSUS INHIBITION OF HEMATOPOIESIS BY 2 CHARACTERIZED STROMALCELL-TYPES

Stromal cells are believed to regulate hematopoiesis through direct ce ll-cell contact interactions and the release of growth factors, Many q uestions remain, however, about their lineage derivation and functiona l heterogeneity. We have previously shown that the adherent nontransfo rmed, nonimmortalized murine bone marrow stromal cell population consi sts of three cell types which could be grown separately in vitro, Base d on the phenotype characterization and expression of surface antigens , we proposed a classification listing for murine bone marrow stromal cells as macrophages, endothelial-like cells and myofibroblasts that d isplay smooth muscle-like characteristics in culture. The present stud y describes the ability of each of these freshly isolated separated mu rine stromal cell populations to support the growth of primitive hemat opoietic stem cells previously characterized as highly enriched in lon g-term repopulating cells (LTRC), Of the three stromal cell types test ed only the myofibroblasts were capable of support for multilineage he matopoiesis derived in vitro from LTRC in a cloning ring culture syste m. Endothelial-like cells had an inhibitory effect on the proliferatio n of LTRC and their descendant cells that was induced by exogenous gro wth factors. This inhibitory activity was present in a low molecular w eight filtrate of endothelial-like cells culture medium. This suggests an essential role for marrow stroma myofibroblasts in the support of proliferation of hematopoietic cells at the stage of early divisions o f primitive hematopoietic stem cells and endothelial-like cells as neg ative regulators of this proliferation.