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

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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.

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Funding Sources

The authors acknowledge support from the National Institutes of Health (NIH 1UH2 TR000506-01, 3UH2 TR000506-02S1, T32 HL007936-12, RO1 HL093282, and R21 EB016381-01).

Conflict of Interest Disclosure

J.A.T. is a founder, stockowner, consultant, and board member of Cellular Dynamics International, Inc. D.A.M., R.L. and C.D. are employed by, and have a financial interest in, Cellular Dynamics International Inc.

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Correspondence to William L. Murphy.

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Belair, D.G., Whisler, J.A., Valdez, J. et al. Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells. Stem Cell Rev and Rep 11, 511–525 (2015). https://doi.org/10.1007/s12015-014-9549-5

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