Kinetic analysis of mechanisms regulating granulopoiesis in cultured human bone marrow

In the past, in vitro perturbations of granulocytic progenitor cells have been measured by comparing the number of colonies that have grown to a threshold size in a given time. In our hands this method has proven to be both insensitive and unreliable. In this paper kinetic evidence is presented that the number of colonies, however defined, is subject to the influence of unpredictable independent variables which include the age distribution of the clonogenic cells, the proportion of them which are dormant, and the factors which promote their recruitment, their expansion into colonies and the rate at which colonies die. Results are improved by an early analysis of total clonal number (TC) as a measure of recruitment and mean clonal size (MCS) as a measure of clonal expansion rate.