The sensitivity of in vitro erythropoietic progenitor cells to different erythropoietin reagents during development and the role of cell death in culture.

Abstract

With the availability of several recombinant erythropoietin (Epo) reagents, it has been possible to undertake a systematic study of the relative Epo sensitivity of late erythroid colony-forming units (CFU-E) in 8.5-day embryos, 13.5-day fetal liver, and adult bone marrow of the mouse. All Epo preparations tested, including one from impure sheep and a highly purified human native Epo preparation, produced parallel, but displaced, dose-response curves when Epo concentration was plotted against percent CFU-E response calculated from the optimal Epo concentration. It was found that the CFU-E derived from 8.5-day embryos demonstrated the greatest Epo sensitivity which decreased in fetal liver and adult bone marrow CFU-E populations. Modifications to the culture system allowed CFU-E to be stimulated with as little as 0.003 mU/mL, equivalent to approximately 0.03 fg Epo. Under these culture conditions, no evidence for apoptosis was found, although a normal programmed cell death function cannot be ruled out.