Regulation of hemopoietic progenitor cell proliferation.

Utilization of appropriate colony scoring criteria allows the identification of subsets of high proliferative potential, but lineage-restricted, erythropoietic and granulopoietic progenitors in human marrow. These cells share with human pluripotent hemopoietic cells the unique ability to vary their proliferative status from a non-cycling (GO) state to a cycling one (continuous progression from G1----S----G2----M). Time course studies of the size and turnover of these primitive, normally quiescent human hemopoietic cell populations in long-term marrow cultures has provided evidence that marrow mesenchymal elements play a role not only in supporting their maintenance, but also in regulating their proliferation. A model delineating how this regulation may be mediated based on known features of mesenchymal cell and hemopoietic progenitor cell biology is presented together with a number of predictions of the model. Preliminary tests are consistent with these. Longterm marrow cultures offer an in vitro system that can be used to analyze how the proliferation of very primitive hemopoietic cells may be controlled by mesenchymal cells. The molecular mechanisms involved may be the same as those that are normally operative in the marrow in vivo and which are de-regulated or by-passed in several human hemopoietic malignancies.