The Florey Lecture, 1991. The colony-stimulating factors: discovery to clinical use

Abstract

The four colony-stimulating factors, GM-GSF, G-CSF, M-CSF and Multi-CSF, are specific glycoproteins with a likely common ancestral origin which interact to regulate the production, maturation and function of granulocytes and monocyte-macrophages. Each has been purified and produced in active recombinant form. Animal studies have shown the ability of injected CSF to increase the production and functional activity of granulocytes and macrophages in vivo and to enhance resistance to infections. These studies have led to the current extensive clinical use of CSFs to promote the formation and function of granulocytes and macrophages in a wide variety of disease situations in which there is an associated risk of serious infections. Although our knowledge of the control of haemopoiesis remains incomplete, the approaches used to develop the CSFs can be used to extend this knowledge, with the promise of the introduction into clinical medicine of additional effective therapeutic agents.

Lineage commitment of hemopoietic progenitor cells in developing blast cell colonies: influence of colony-stimulating factors.

“…These progenitor cells have a blast cell morphology and are heterogeneous in their proliferative potential but most appear to have undergone irreversible lineage commitment and to have no capacity for self generation (1). Murine progenitor cells committed to the granulocyte-macrophage lineage can form colonies of granulocytes and/or macrophages and are responsive in various degrees to proliferative stimulation by at least six defined hemopoietic regulators: granulocytemacrophage, granulocyte, macrophage, and multipotential (or interleukin 3) colony-stimulating factors (GM-CSF, G-CSF, M-CSF, and multi-CSF, respectively), interleukin 6, and the stem cell factor (SCF) (also known as mast cell growth factor, kit ligand, or Steel factor) (2).…”

Synergistic suppression: anomalous inhibition of the proliferation of factor-dependent hemopoietic cells by combination of two colony-stimulating factors.

“…What may be a comparable suppression has also been observed with normal macrophage colonies (2,3), and the mechanisms responsible need to be clarified, if for no other reason than that the CSFs are in clinical use and there are general grounds for proposing their use in combination (14). Finally, the present suppressive phenomenon is remarkably similar to the unusual ability of the CSFs, alone or in combination, to suppress the clonogenic proliferation of certain myeloid leukemic cell lines (15,16).…”

Genomics and proteomics in stem cell research: the road ahead

“…According to Metcalf, one of the pioneers of CSF research, the most formidable technical challenge in identifying CSFs was their purification (Metcalf 1991). Given the current status of proteomics technology, a project like that of CSF purification and identification can now be completed in six months rather than years or decades.…”