Cell kinetic status of haematopoietic stem cells

The haematopoietic stem cell (HSC) population supports a tremendous cellula r production over the course of an animal's lifetime, e.g. adult humans pro duce their body weight in red cells, white cells and platelets every 7 year s, while the mouse produces about 60% of its body weight in the course of a 2 year lifespan. Understanding how the HSC population carries this out is of interest and importance, and a first step in that understanding involves the characterization of HSC kinetics. Using previously published continuou s labelling data (of Bradford er nl. 1997 and Cheshier et al. 1999) from mo use HSC and a standard G(o) model for the cell cycle, the steady state para meters characterizing these HSC populations are derived. It is calculated t hat in the mouse the differentiation rate ranges between about 0.01 and 0.0 2. the rate of cell re-entry from G(o) back into the proliferative phase is between 0.02 and 0.05, the rate of apoptosis from the proliferative phase is between 0.07 and 0.23 (all units are days(-1)), and the duration of the proliferative phase is between 1.4 and 4.3 days. These values are compared with previously obtained values derived from the modelling by Abkowitz and colleagues of long-term haematopoietic reconstitution in the cat (Abkowitz ef cbl. 1996) and the mouse (Abkowitz et al. 2000). It is further calculate d using the estimates derived in this paper and other data on mice that bet ween the HSC and the circulating blood cells there are between 17 and 19.5 effective cell divisions giving a net amplification of between similar to 1 70 000 and similar to 720 000.