Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro

J Vasc Res. 2018;55(1):13-25. doi: 10.1159/000481779. Epub 2017 Dec 2.

Abstract

Background/aims: Platelets affect endothelial progenitor cell (EPC) functionality, inducing their differentiation into mature endothelial cells. However, it remains to be established whether EPCs can influence platelet functionality.

Methods: Mononuclear proangiogenic cells (MPCs) and early outgrowth cells (EOCs) were prepared from peripheral blood mononuclear cells, whereas late-outgrowth endothelial cells (OECs) were prepared from cord blood CD34+ cells. The effect of the above cells and their supernatants on washed platelet aggregation was studied. The effect of OECs and their supernatant on the adenosine diphosphate (ADP)-induced magnitude of platelet integrin receptor αIIbβ3 activation and on P-selectin membrane expression was investigated. The levels of nitric oxide (NO) and prostacyclin (PGI2) that were secreted from EOCs, OECs, and human umbilical vein endothelial cells (HUVECs) were also assessed.

Results: Among all progenitors, OECs and their supernatant exhibited the most potent inhibitory activity towards platelet aggregation. Furthermore, OECs and their supernatant, but not CD34+ cells, reduced αIIbβ3 activation and P-selectin membrane expression. Finally, OECs secreted higher NO and PGI2 levels than EOCs did.

Conclusion: The anti-platelet effect of EPCs depends highly on the degree of their endothelial phenotype, with OECs expressing the highest potency. Therefore, the induction of OEC generation and the enhancement of their functionality in vivo could be a new approach for the treatment of patients at a high thrombotic risk.

Keywords: CD34+ cells; Endothelial cells; Endothelial progenitor cells; Human umbilical vein endothelial cells; Late-outgrowth endothelial cells; Nitric oxide; Platelet activation; Platelets; Prostacyclin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / metabolism*
  • Blood Platelets / metabolism*
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Endothelial Progenitor Cells / metabolism*
  • Epoprostenol / metabolism
  • Female
  • Fetal Blood / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Nitric Oxide / metabolism
  • P-Selectin / metabolism
  • Phenotype
  • Platelet Aggregation*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Pregnancy
  • Signal Transduction
  • Time Factors

Substances

  • Antigens, CD34
  • Culture Media, Conditioned
  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • SELP protein, human
  • Nitric Oxide
  • Epoprostenol