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Cell Transplant. 2017 Mar 9. doi: 10.3727/096368916X695236. [Epub ahead of print]

Engineered microvasculature in PDMS networks using endothelial cells derived from human induced pluripotent stem cells.

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Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Anesthesiology, Yale University, New Haven, CT, USA.
Section of Comparative Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA.
Department of Medicine, Section of Cardiovascular Medicine, Yale University, New Haven, CT, USA.


In this study, we used a PDMS-based platform for the generation of intact, perfusioncompetent microvessel networks <i>in vitro</i>. COMSOL Multiphysics, a finite element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human iPSCs were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 days under completely chemically defined conditions, using the small molecule GSK3β inhibitor CHIR99021 and thoroughly characterized for functionality and arteriallike marker expression. These cells, along with primary human umbilical vein endothelial cells (HUVECs), were seeded in the PDMS system to generate microvascular networks that were subjected to shear stress. Engineered microvessels had patent lumens and expressed VE-cadherin along their periphery. Shear stress caused by flowing medium increased the secretion of nitric oxide (NO), caused ECs to align and to re-distribute actin filaments parallel to the direction of the laminar flow. Shear stress also caused significant increases in gene expression for arterial markers Notch1 and EphrinB2, as well as anti-thrombotic markers KLF-2/KLF-4. These changes in response to shear stress in the microvascular platform were observed in hiPSC-EC microvessels, but not in microvessels that were derived from HUVECs, which indicated that hiPSC-ECs may be more plastic in modulating their phenotype under flow than are HUVECs. Taken together, we demonstrate the feasibly of generating intact, engineered microvessels <i>in vitro</i>, which replicate some of the key biological features of native microvessels.

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