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Blood, 1 February 2004, Vol. 103, No. 3, pp. 921-926.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-04-1284.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Erythropoietin regulates endothelial progenitor cells
Ferdinand H. Bahlmann,
Kirsten de Groot,
Jens-Michael Spandau,
Aimee L. Landry,
Barbara Hertel,
Thorsten Duckert,
Sascha M. Boehm,
Jan Menne,
Hermann Haller, and
Danilo Fliser
From the Division of Nephrology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany; and Phenos GmbH, Hannover, Germany.
Circulating bone marrow–derived endothelial progenitor cells (EPCs) promote vascular reparative processes and neoangiogenesis, and their number in peripheral blood correlates with endothelial function and cardiovascular risk. We tested the hypothesis that the cytokine erythropoietin (EPO) stimulates EPCs in humans. We studied 11 patients with renal anemia and 4 healthy subjects who received standard doses of recombinant human EPO (rhEPO). Treatment with rhEPO caused a significant mobilization of CD34+/CD45+ circulating progenitor cells in peripheral blood (measured by flow cytometry), and increased the number of functionally active EPCs (measured by in vitro assay) in patients (week 2, 312% ± 31%; week 8, 308% ± 40%; both P < .01 versus baseline) as well as in healthy subjects (week 8, 194% ± 15%; P < .05 versus baseline). The effect on EPCs was already observed with an rhEPO dose of about 30 IU/kg per week. Administration of rhEPO increased the number of functionally active EPCs by differentiation in vitro in a dose-dependent manner, assessed in cell culture and by tube formation assay. Furthermore, rhEPO activates the Akt protein kinase pathway in EPCs. Erythropoietin increases the number of functionally active EPCs in humans. Administration of rhEPO or EPO analogs may open new therapeutic strategies in regenerative cardiovascular medicine.
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