Colonystimulating Factors

John W Schrader, The Biomedical Research Centre, UBC, Vancouver, Canada

Colony-stimulating factor (CSF) is the operational term for a class of molecules that stimulate hematopoietic progenitor cells to divide and generate colonies of differentiated progeny such as neutrophils or macrophages. Colony-stimulating factors were originally detected and assayed by culturing a source of hematopoietic progenitor cells, such as a cell suspension derived from the bone marrow, in medium that has been jellified by the addition of a substance such as agar or methyl cellulose. Provided a CSF or a source of a CSF is present, hematopoietic progenitors survive and grow, and over a period of a week or so, give rise to colonies of 100-10 000 differentiated cells. The number of colonies and the extent to which a preparation can be diluted and still retain activity, can be used to quantitate the CSFs in that preparation. Moreover the morphology of the differentiated cells in the colonies can be determined by picking off and staining the colonies or by staining the whole culture.

Colony assays were developed in the 1960s by Pluznik and Sacks and Bradley and Metcalf, and have in large part provided the data that have generated our current picture of the molecular regulation of hematopoiesis and of the cellular steps in the differentiation of hematopoietic cells. Colony assays also have allowed the identification of different types of committed progenitor cells and determination of their physical and antigenic characteristics.

All CSFs share three basic properties:

1 they support the survival of hematopoietic progenitor cells and mature cells such as neutrophils by suppressing apoptosis;

2 they stimulate growth of stem/progenitor cells and in some cases of mature cells, e.g. mast cells or macrophages;

3 they regulate the function of cells, for example activating mature granulocytes.

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