Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis

Abstract

The proliferation and development of haemopoietic stem cells takes place in close association with marrow stromal cells^1,2. This intimate cell contact presumably enables the stem cells and their progeny to respond to stimuli present on the stromal cell surface. While the nature of these stimuli has not been determined, it is likely that growth factors play some role. Recently, it was demonstrated that the natural and the recombinant haemopoietic growth factor, granulocyte/macrophage colony stimulating factor (GM-CSF), could be adsorbed out of solution by an extract of human marrow stromal extracellular matrix (ECM) with retention of biological activity³. However, the precise ECM molecules involved were not identified. Here, we clearly demonstrate that the major sulphated glycosaminoglycan of mouse marrow stroma, heparan sulphate⁴, possesses the ability to adsorb both GM-CSF and the multilineage haemopoietic growth factor, Interleukin 3 (IL-3). Furthermore, these growth factors, once bound, can be presented in the biologically active form to haemopoietic cells.