CONTROL OF STROMA-DEPENDENT HEMATOPOIESIS BY BASIC FIBROBLAST GROWTH-FACTOR - STROMAL PHENOTYPIC PLASTICITY AND MODIFIED MYELOPOIETIC FUNCTIONS

It has been suggested that basic fibroblast growth factor (bFGF) affec ts hematopoietic cells directly and that it may also act indirectly by modulating stromal cell functions. We tested the response of phenotyp ically and functionally distinct stromal cell clones to this cytokine. We studied cell phenotype, the composition and organization of cytosk eleton and extracellular matrix, the ability to repopulate 'wounded ar eas', the expression of cytokine genes, and the capacity of the stroma to support long-term hematopoiesis in vitro. Although the impact of b FGF on cell growth was small, it induced a prominent morphological cha nge in three stromal cell types that we tested. We analyzed the molecu lar basis for this change: bFGF modified the protein expression of a-s mooth muscle actin (alpha-SMA), tropomyosin, a-tubulin, fibronectin an d paxillin in a distinct manner characteristic of each of the stromal cell types. Immunofluorescence analysis of these proteins revealed pro found changes in the cytoskeleton and extracellular matrix (ECM) netwo rks accompanied by increased ability of the 14F1.1 stromal cells to sc atter in in vitro 'wounded' areas. Furthermore, although only limited changes were monitored in the expression of cytokine genes, the abilit y of the stromal cells to support hematopoiesis was markedly modified. Thus bFGF profoundly changes the cellular organization of stromal cel ls, their adhesion and their motility properties. These changes are as sociated with modified capacity to support hematopoiesis in culture.