Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin.
BACKGROUND
Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular reparative processes. In humans, their number correlate with endothelial function and cardiovascular risk. We tested the hypothesis that darbepoetin alfa [i.e., a recombinant analogue of the cytokine erythropoietin (EPO)] stimulates proliferation and differentiation of EPCs.


METHODS
We assessed CD34+ circulating stem cells (cSCs) in whole blood using flow cytometry and, in addition, proliferation/differentiation of EPCs in an in-vitro assay during 6 weeks of a standard darbepoetin therapy in eight patients with renal anemia.


RESULTS
Darbepoetin treatment caused a significant increase in the number of CD34+ cSCs (week 2, 193%+/- 46%; and week 6, 298%+/- 90%; P < 0.05 vs. baseline). In addition, darbepoetin markedly increased the number of functionally active EPCs (week 2, 256%+/- 48%; and week 6, 299%+/- 59%; both P < 0.01 vs. baseline). The effect of darbepoetin on functional activity of EPCs assessed in a tube formation assay was dose dependent. Administration of darbepoietin caused activation of protein kinase B (Akt) in cultured EPCs.


CONCLUSIONS
A standard treatment with darbepoetin markedly enhances EPC proliferation and differentiation in renal patients. The use of recombinant EPO analogues may be a novel and safe therapeutic approach in patients with vascular pathology.
Bahlmann
Ferdinand H
FH
Division of Nephrology, Department of Internal Medicine, Hanover Medical School, Hanover, Germany. Bahlmann.Ferdinand@MH-Hannover.de
DeGroot
Kirsten
K
Duckert
Thorsten
T
Niemczyk
Eva
E
Bahlmann
Elisabeth
E
Boehm
Sascha M
SM
Haller
Hermann
H
Fliser
Danilo
D
D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000068256:Darbepoetin alfa; D004727:Endothelium / Q000166:cytology; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D005434:Flow Cytometry; D006400:Hematocrit; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged
D004921:Erythropoietin; D000068256:Darbepoetin alfa