Effects of erythropoietin on erythroid colony formation in uremic rabbit bone marrow cultures

Erythropoietin-responsive stem cell (ERC) kinetics in anephric uremic rabbits were studied in vitro using the growth of erythroid colonies in a methyl cellulose system in cultures with and without the addition of erythropoietin (ESF). Approximately 68 hr after bilateral nephrectomy, an increase in BUN and decreases in hematocrit and marrow erythroid cellularity were seen. However, the numbers of erythroid colonies formed in response to ESF on plates inoculated with 2 times 10-5 cells were greater in anephric rabbit marrows than in normal controls. In addition, the numbers of erythroid colonies produced by the uremic and normal marrows in the presence of ESF were increased in proportion to the number of precursors plated. These findings suggest that, in uremia, the concentration of ERC is increased and that the ERC are capable of responding normally to ESF. The increase in the number of erythroid colonies of uremia may be due to the undisturbed flow of uncommitted hematopoietic stem cells into the ERC compartment in the presence of a delay of differentiation of ERC into heme-synthesizing nucleated erythroid cells due to a lack of ESF.