Evaluation of epoetin alpha (rHuEPO) and darbepoetin alpha (DARB) on human burst-colony formation (BFU-E) in culture.
The erythropoietic effect of recombinant human erythropoietin, epoetin alpha (rHuEPO), in promoting the growth of erythroid burst-forming units (BFU-E) was compared with darbepoetin alpha (DARB), a rHuEPO analogue obtained by site-directed mutagenesis. Human bone marrow cells derived from healthy donors were cultured with different concentrations of rHuEPO or DARB for 12 - 21 days and BFU-E were counted using an inverted microscope. The EC50 of rHuEPO was about 10-fold lower than DARB and the size of the colonies was significantly larger in rHuEPO-containing cultures using comparable concentrations. The maximum number of colonies obtained in some rHuEPO-containing cultures was also higher than for DARB. The number of colonies in DARB-containing cultures was increased, in part, by the addition of low concentrations of rHuEPO, but not by DARB, even at high concentrations. We conclude that DARB is not as effective as rHuEPO in supporting the in vitro growth of human BFU-E.
Jamal
N M
NM
University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada. nazir@uhnres.utoronto.ca
Krzyzanski
W
W
Cheung
W
W
Lau
C Y
CY
Messner
H A
HA
D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins; D013997:Time Factors
D006133:Growth Substances; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa