Assessing the ability of human endothelial cells derived from induced-pluripotent stem cells to form functional microvasculature in vivo

Biotechnol Bioeng. 2019 Feb;116(2):415-426. doi: 10.1002/bit.26860. Epub 2018 Dec 9.


Forming functional blood vessel networks is a major clinical challenge in the fields of tissue engineering and therapeutic angiogenesis. Cell-based strategies to promote neovascularization have been widely explored, but cell sourcing remains a significant limitation. Induced-pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising, potentially autologous, alternative cell source. However, it is unclear whether iPSC-ECs form the same robust microvasculature in vivo documented for other EC sources. In this study, we utilized a well-established in vivo model, in which ECs (iPSC-EC or human umbilical vein endothelial cells [HUVEC]) were coinjected with normal human lung fibroblasts (NHLFs) and a fibrin matrix into the dorsal flank of severe combined immunodeficiency mice to assess their ability to form functional microvasculature. Qualitatively, iPSC-ECs were capable of vessel formation and perfusion and demonstrated similar vessel morphologies to HUVECs. However, quantitatively, iPSC-ECs exhibited a two-fold reduction in vessel density and a three-fold reduction in the number of perfused vessels compared with HUVECs. Further analysis revealed the presence of collagen-IV and α-smooth muscle actin were significantly lower around iPSC-EC/NHLF vasculature than in HUVEC/NHLF implants, suggesting reduced vessel maturity. Collectively, these results demonstrate the need for increased iPSC-EC maturation for clinical translation to be realized.

Keywords: HUVECs; endothelial cell; iPSCs; vascularization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Endothelial Cells / physiology*
  • Fibrin / metabolism
  • Fibroblasts / physiology
  • Histocytochemistry
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Mice, SCID
  • Neovascularization, Physiologic*


  • Fibrin