- Objective Burst-forming unit erythroid and colony-forming unit erythroid growth in vitro is lower in studies of continuous ambulatory peritoneal dialysis patients than healthy controls. Burst-forming unit erythroid growth was potentiated by addition of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and normalized by erythropoietin (Epo) therapy, suggesting an interaction between Epo and 1,25(OH)2D3 at the stem cell level. The objective of this study was to determine the mechanism by which 1,25(OH)2D3 enhances the stimulatory effect of Epo on the growth of erythroid precursor cells. Materials and Methods We examined the effect of 1,25(OH)2D3 and Epo on stem cell proliferation. Proliferation of TF1 cells of erythroid origin was measured by the XTT method, 3[H] thymidine incorporation, and cell counting by trypan blue exclusion; cord blood (CB) stem cells were counted. Epo receptor (EpoR) quantitation was evaluated by 125I-Epo binding and Scatchard analysis, immunoprecipitation, and Western blotting. Expression of EpoR mRNA was measured by reverse transcriptase polymerase chain reaction. Results The stem cell factor-dependent CB stem cells and the TF1 cells responded to Epo and 1,25(OH)2D3 by increased proliferation, while their simultaneous addition potentiated cell proliferation in a synergistic manner (25.67% ± 4.8% of Epo proliferation at day 10 for CB cells; p < 0.005). 1,25(OH)2D3 produced an up-regulation of EpoR number in TF1 cells and increased the expression of EpoR mRNA (p < 0.01). Conclusions The increase in EpoR expression induced by 1,25(OH)2D3 might explain the synergistic interaction between Epo and 1,25(OH)2D3 in stem cells.