Kinetic Parameters of Bone Marrow Stem Cells Using In Vivo Suicide by Tritiated Thymidine or by Hydroxyurea

The kinetics of colony-forming units (CFU) of the bone marrow in mice were studied using a method involving the suicide of cells in vivo by ³H-TdR or hydroxyurea. After selectively killing cells in S phase, the surviving cells traversed S phase in a cyclic fashion. This enabled the duration of the cycle and of the S phase of CFU to be measured—8 hr and 4 hr, respectively. It was shown that quiescent stem cells pass into the proliferative compartment. A computer model helped to explain the experimental results. The feedback mechanism seemed to be initiated by the depletion of the compartment of maturing cells. This hypothesis is supported by the fact that the CFU response to S-phase cell killing was similar in two strains of mice and was independent of the proportion of CFU in S phase, which was approximately 0% in the C57BI and 20% in the C3H mice.