Initial clonogenic potential of human endothelial progenitor cells is predictive of their further properties and establishes a functional hierarchy related to immaturity

Stem Cell Res. 2017 May;21:148-159. doi: 10.1016/j.scr.2017.04.009. Epub 2017 Apr 21.

Abstract

Endothelial progenitor cells (EPCs) generate in vitro Endothelial Colony Forming Cells (ECFCs) combining features of endothelial and stem/progenitor cells. Their angiogenic properties confer them a therapeutic potential for treating ischemic lesions. They may be isolated from umbilical cord blood (CB-ECFCs) or peripheral adult blood (AB-ECFCs). It is generally accepted that CB-ECFCs are more clonogenic, proliferative and angiogenic than AB-ECFCs. Nevertheless, only a few studies have focused on the functional heterogeneity of CB-ECFCs from different individuals. Moreover, AB-ECFC loss of function is yet to be precisely described. We have focused on these two issues that are critical for clinical perspectives. The detailed clonogenic profile of CB-ECFCs and AB-ECFCs was obtained and revealed a high inter individual heterogeneity and the absence of correlation with age. Most CB-ECFCs yielded initial colonies and had functional properties similar to those of AB-ECFCs. Conversely, a high clonogenicity was associated with an enhanced proliferative and angiogenic potential and stemness gene overexpression, confirming that immaturity, lost by AB-ECFCs, was a prerequisite to functionality. We thus demonstrated the importance of selecting CB-ECFCs according to specific criteria, and we propose using the initial clonogenicity as a relevant marker of their potential efficacy on vascular repair.

Keywords: Cord blood; Endothelial Colony Forming Cells; Endothelial progenitor cells; Functional hierarchy; Immaturity; Peripheral adult blood; Senescence.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antigens, CD34 / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation* / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Clone Cells
  • Collagen / pharmacology
  • Colony-Forming Units Assay
  • Drug Combinations
  • Endothelial Progenitor Cells / cytology*
  • Endothelial Progenitor Cells / drug effects
  • Endothelial Progenitor Cells / metabolism
  • Fetal Blood / cytology
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology
  • Laminin / pharmacology
  • Male
  • Middle Aged
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type III / metabolism
  • Proteoglycans / pharmacology
  • Tissue Donors
  • Young Adult

Substances

  • Antigens, CD34
  • Biomarkers
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Nitric Oxide
  • Collagen
  • Nitric Oxide Synthase Type III