Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment

Haematopoietic progenitor cells proliferate and mature in semi-solid media when stimulated by exogenous haematopoietic cell growth factors (HCGFs) such as granulocyte-macrophage colony-stimulating factor (GM-CSF)1,2. They also proliferate in association with marrow-derived stromal cells3,4 although biologically active amounts of HCGFs cannot be detected in stromal culture supernatants5. It is possible that HCGFs are synthesized in small amounts by stromal cells but remain bound to the stromal cells and/or their extracellular matrix (ECM). This interpretation accords with haematopoietic progenitor cell proliferation in close association with stromal layers in long-term cultures6. Glycosaminoglycans (GAGs) are found in the ECM produced by stromal cells27,8. They are prime candidates for selectively retaining HCGFs in the stromal layer9; they influence embryonic morphogenesis and cyto-differentiation10 and they may regulate hamatopoiesis11-13. We now report that granulocyte- macrophage colony-stimulating activity can be eluted from cultured stromal layers and that exogenous GM-CSF binds to GAGs from bone marrow stromal ECM. Selective Compartmentalization of HCGFs in this manner may be an important function of the marrow microenvironment and may be involved in haematopoietic cell regulation. © 1987 Nature Publishing Group.