Stem Cell Reviews and Reports

, Volume 11, Issue 3, pp 511–525 | Cite as

Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

  • David G. Belair
  • Jordan A. Whisler
  • Jorge Valdez
  • Jeremy Velazquez
  • James A. Molenda
  • Vernella Vickerman
  • Rachel Lewis
  • Christine Daigh
  • Tyler D. Hansen
  • David A. Mann
  • James A. Thomson
  • Linda G. Griffith
  • Roger D. Kamm
  • Michael P. Schwartz
  • William L. Murphy
Article

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.

Keywords

Stem cell Induced pluripotent stem cell Endothelial cell Angiogenesis Vascular model Vascular function Tubulogenesis Migration Sprouting Barrier function 

Supplementary material

12015_2014_9549_MOESM1_ESM.pptx (462 kb)
ESM 1(PPTX 461 kb)
12015_2014_9549_MOESM2_ESM.pptx (7.8 mb)
ESM 2(PPTX 8037 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David G. Belair
    • 1
  • Jordan A. Whisler
    • 2
  • Jorge Valdez
    • 3
  • Jeremy Velazquez
    • 3
  • James A. Molenda
    • 1
  • Vernella Vickerman
    • 4
  • Rachel Lewis
    • 5
  • Christine Daigh
    • 5
  • Tyler D. Hansen
    • 1
  • David A. Mann
    • 5
  • James A. Thomson
    • 4
    • 6
    • 7
  • Linda G. Griffith
    • 3
  • Roger D. Kamm
    • 2
    • 3
  • Michael P. Schwartz
    • 1
  • William L. Murphy
    • 1
    • 8
    • 9
    • 10
  1. 1.Department of Biomedical EngineeringUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of Mechanical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Morgridge Institute for ResearchMadisonUSA
  5. 5.Cellular Dynamics International, Inc.MadisonUSA
  6. 6.Department of Cell and Regenerative BiologyUniversity of Wisconsin-MadisonMadisonUSA
  7. 7.Department of Molecular Cellular and Developmental BiologyUniversity of California-Santa BarbaraSanta BarbaraUSA
  8. 8.Material Science ProgramUniversity of Wisconsin-MadisonMadisonUSA
  9. 9.Department of Orthopedics and RehabilitationUniversity of Wisconsin-MadisonMadisonUSA
  10. 10.Wisconsin Institute for Medical ResearchMadisonUSA

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