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

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

Author information

1
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.

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.

PMID:
25190668
PMCID:
PMC4411213
DOI:
10.1007/s12015-014-9549-5
[Indexed for MEDLINE]
Free PMC Article

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