Mathematical analysis of bone marrow erythropoiesis: application to C3H mouse data

A mathematical analysis of normal bone marrow erythropoiesis is investigated under the following assumptions: there is no correlation for a cell between its position in cell cycle and its maturation level; the transition between proliferant and quiescent cells along the erythroid line occurs at a critical point in its cell cycle when a certain maturation level is reached; there is no net migration between the bone marrow and other hemopoietic tissues. Relationships are derived between model parameters (cell flows and cell number) and kinetic parameters, namely, the classic proliferation parameters (cell cycle time duration and growth fraction) and the maturation parameters (maturation time duration and amplification coefficient). This model, when applied to normal C3H mouse experimental data, provides a complete description of bone marrow erythropoiesis from pluripotent stem cells up to mature red blood cells. No differentiation from the pluripotent stem cells to the erythroid line is necessary to explain our experimental data. The number of erythroid-committed stem cells is estimated to be 3.4 x 10(5). Their maturation is characterized by eight divisions and a transit duration time of approximately 2.5 days. No ineffective erythropoiesis is found. Moreover, important red blood cell production is found in some other hemopoietic tissues. The 55Fe-labeling experiment of proerythroblasts is interpreted, assuming variability among cells for cell cycle and maturation time durations. For our experimental data, neglecting such a variability jeopardizes parameter estimations for proerythroblast population.