Increased erythropoietin sensitivity of murine CFU-E and BFU-E in in vivo cultures

The in vivo PCDC assay was used to reassess the erythropoietin requirements for growth in culture of the erythroid precursor cells CFU-E and BFU-E. Both CFU-E and BFU-E are expressed with the physiologically low erythropoietin concentrations present in normal host mice. Moreover, the same number of CFU-E-derived colonies is observed in hypertransfused host animals. No BFU-E are observed under these conditions. Increased numbers of both CFU-E and BFU-E are expressed in anemic host animals; these values are moderately lower than those found with in vitro cultures containing large concentrations of erythropoietin. Thus, at high levels of erythropoietin, the in vivo PCDC assay appears to be somewhat less sensitive than conventional in vitro assays. However, this culture system is more sensitive at low levels of erythropoietin and demonstrates a much smaller erythropoietin requirement for the differentiation of both CFU-E and BFU-E than has hitherto been recognized. This is as should be expected if these progenitor cells play a role in normal erythropoiesis in vivo. Experiments concerning the effects of anemia or hypertransfusion in donor rather than host mice reconfirm that the population size in the marrow of CFU-E but not BFU-E is highly sensitive to erythropoietin. However, phenylhydrazine treatment of donor mice leads to the transient development of a new subclass of BFU-E which gives rise to colonies relatively late in culture, suggesting that erythropoietin does have a direct effect on the physiological status of BFU-E in the bone marrow.