Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells

Nat Biotechnol. 2014 Nov;32(11):1151-1157. doi: 10.1038/nbt.3048. Epub 2014 Oct 12.


The ability to differentiate human pluripotent stem cells into endothelial cells with properties of cord-blood endothelial colony-forming cells (CB-ECFCs) may enable the derivation of clinically relevant numbers of highly proliferative blood vessel-forming cells to restore endothelial function in patients with vascular disease. We describe a protocol to convert human induced pluripotent stem cells (hiPSCs) or embryonic stem cells (hESCs) into cells similar to CB-ECFCs at an efficiency of >10(8) ECFCs produced from each starting pluripotent stem cell. The CB-ECFC-like cells display a stable endothelial phenotype with high clonal proliferative potential and the capacity to form human vessels in mice and to repair the ischemic mouse retina and limb, and they lack teratoma formation potential. We identify Neuropilin-1 (NRP-1)-mediated activation of KDR signaling through VEGF165 as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Embryonic Stem Cells / cytology*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Fetal Blood / cytology
  • Humans
  • Mice
  • Neuropilin-1 / metabolism
  • Pluripotent Stem Cells / cytology*
  • Stem Cells / cytology
  • Vascular Endothelial Growth Factor A / metabolism


  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1

Associated data

  • GEO/GSE49074