In vivo erythropoietin requirements of regenerating erythroid progenitors (BFU-e, CFU-e) in bone marrow of mice

Erythroid progenitors (B-8, B-4, CFU-e) in the femoral marrow of polycythemic mice were measured by in vitro culture assays after a single administration of BCNU or Myleran. BCNU reduced pluripotent stem cells to 40% and erythroid progenitors to less than 5% of normal. B-8, the earliest erythroid progenitors, regenerated without erythropoietin (Epo) completely within 5 days. At 14 days after BCNU, intermediate progenitors (B-4) attained 60% of their normal numbers and CFU-e attained approximately 30%. Daily injections of Epo promptly restored normal B-4 numbers and near-normal CFU-e numbers in BCNU-treated mice. After Myleran, CFU-s remained below 2% of normal for 14 days, and no regeneration of the B-8 occurred with or without daily Epo injections. The findings suggest that regneration of B-8 was dependent on cell inflow from the pluripotent stem cell compartment but was independent of the presence of Epo. Intermediate progenitors (B-4) required Epo and the presence of B-8 for complete and permanent regeneration. CFU-e were the most Epo-dependent of the three progenitors. B-4, recruited by Epo, required after their formation a second exposure to the hormone in order to progress into the CFU-e stage.