The Hemopoietic Growth Factor, Granulocyte-Macrophage Colony Stimulating Factor

Abstract

The notion that soluble growth factors are, at least in part, responsible for regulating the proliferation and differentiation of hemopoietic cells was substantiated in 1906 with the discovery of erythropoietin, a molecule required for the final stages of maturation of erythroid cells. However, the identification of factors acting on myeloid cells had to await the development in the mid 1960s of techniques for the clonal culture of such cells in vitro (Pluznick and Sachs 1965; Bradley and Metcalf 1966). In such culture systems, hemopoietic progenitor cells (typically from adult bone marrow or foetal liver) plated in semi-solid cultures give rise to colonies of normal hemopoietic cells if a source of factor stimulating their development is present - hence the operational term for such factors: colony stimulating factors (CSFs). In the mid 1960s fairly complex sources of such factors were used; pokeweed mitogen-stimulated spleen conditioned medium, for example. However, in the past two decades many of the active factors in such broths have been biologically characterized, biochemically purified and molecularly cloned (see Metcalf 1984, 1987 for reviews). Indeed, several hemopoietic growth factors are currently undergoing various clinical trials and face an exciting therapeutic future.