Regulation of erythropoiesis. XX. Kinetics of red cell production.

TLDR: Data is presented on the effect of erythropoietin in normal animals and in rats in which red cell production has been perturbed by hypertransfusion and/or vincristine and critical to these considerations are studies on megakaryocytopoiesis using tritiated thymidine.

Abstract: Since the last conference on erythropoiesis, much information has accumulated which has necessitated a revision of some of our notions as to the mechanism of red cell formation. It is still clear that the erythroid compartment is not a self-maintaining compartment, but is fed from a primitive stem cell pool. The work of Becker et a1.I and Whang et aL2 appeared to settle the long standing issue whether this is a unipotential or totipotential compartment. More recent evidence, however, raises the question as to whether there may not be two levels of stem cells, a more primitive totipotential stem cell compartment equivalent to the colony-forming unit of Till and McCulloch3 and a more differentiated precursor cell for each of the identifiable hematopoietic elements. This issue is by no means settled, but data will be presented favoring the latter explanation, i.e., two levels of precursor cells. The studies on the effect of erythropoietin in the hypertransfused rodent clearly demonstrated that erythropoietin is capable of differentiating the stem cell into an identifiable erythroid precursor. The mechanism by which this is accomplished is moot and the question of whether the action of erythropoietin is confined to the stem cell or whether it may also affect differentiated cells is at present undecided. In this paper it is our purpose to present data bearing on these points. The effect of erythropoietin has been studied in normal animals and in rats in which red cell production has been perturbed by hypertransfusion and/or vincristine. Critical to these considerations are studies on megakaryocytopoiesis using tritiated thymidine. These also will be reported briefly.