title: Human vascular tissue models formed from human induced pluripotent stem cell derived endothelial cells.
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.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Belair
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Whisler
authors.forename: Jorge
authors.initials: J
authors.lastname: Valdez
authors.forename: Jeremy
authors.initials: J
authors.lastname: Velazquez
authors.forename: James A
authors.initials: JA
authors.lastname: Molenda
authors.forename: Vernella
authors.initials: V
authors.lastname: Vickerman
authors.forename: Rachel
authors.initials: R
authors.lastname: Lewis
authors.forename: Christine
authors.initials: C
authors.lastname: Daigh
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Hansen
authors.forename: David A
authors.initials: DA
authors.lastname: Mann
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schwartz
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
mesh_terms: D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D018919:Neovascularization, Physiologic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A