Increased total number but impaired migratory activity and adhesion of endothelial progenitor cells in patients on long-term hemodialysis

Am J Kidney Dis. 2004 Nov;44(5):840-9.


Background: Endothelial progenitor cells (EPCs), derived from bone marrow, contribute to vessel repair and neovascularization. Because uremia is a state of endothelial dysfunction associated with high cardiovascular mortality, as well as a state of reduced hematopoiesis, we studied the number and function of EPCs in patients on long-term hemodialysis (HD) therapy.

Methods: We counted the number of EPCs in 20 HD patients and 16 healthy volunteers. To assess EPC function, we measured migratory activity, adhesion to matrix proteins, and adhesion to endothelial cells. Furthermore, we measured blood levels of vascular endothelial growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor, factors known to influence EPC kinetics. Circulating precursor cells (CD34+ , CD34+ /CD133+ , CD34+ /KDR+ cells) were counted by means of flow cytometric analysis.

Results: The number of EPCs in HD patients was significantly elevated compared with controls (459.7 +/- 92 versus 364.8 +/- 77.4 EPC/high-power field). However, migratory activity was markedly decreased in HD patients (47.5 +/- 27.7 versus 84.7 +/- 3.2 EPC/high-power field). EPCs of HD patients showed impaired adhesion to extracellular matrix and endothelial cells. VEGF blood levels in HD patients were 2-fold greater compared with controls. The number of circulating CD34+ and CD34+ /133+ cells was reduced in HD patients. There were no differences in total numbers of CD34+ /KDR+ cells.

Conclusion: This study shows an elevated number, but pronounced functional impairment, of EPCs in patients on long-term HD therapy. The latter may result in limited endothelial repair, which, in turn, may contribute to endothelial dysfunction in this particular group of patients.

MeSH terms

  • AC133 Antigen
  • Adult
  • Antigens, CD
  • Antigens, CD34 / biosynthesis
  • Apoptosis / physiology
  • Cell Adhesion / physiology*
  • Cell Count
  • Cell Movement / physiology*
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Coronary Vessels / metabolism
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Endothelium, Vascular / cytology
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Flow Cytometry / methods
  • Glycoproteins / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Humans
  • Leukocytes, Mononuclear / physiology
  • Male
  • Peptides
  • Renal Dialysis / methods*
  • Stem Cells / chemistry
  • Stem Cells / metabolism*
  • Stem Cells / pathology*
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
  • Vascular Endothelial Growth Factors / blood


  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Extracellular Matrix Proteins
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Vascular Endothelial Growth Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Vascular Endothelial Growth Factor Receptor-2