Human vascular tissue models formed from human induced pluripotent stem cell derived endothelial cells

Stem Cell Rev Rep. 2015 Jun;11(3):511-25. doi: 10.1007/s12015-014-9549-5.

Abstract

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats.

Publication types

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

MeSH terms

  • Blood Vessels / growth & development*
  • Blood Vessels / metabolism
  • Cell Differentiation / genetics*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Induced Pluripotent Stem Cells*
  • Neovascularization, Physiologic / genetics*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A