Functional brain-specific microvessels from iPSC-derived human brain microvascular endothelial cells: the role of matrix composition on monolayer formation

Fluids and Barriers of the CNS
Moriah E KattPeter C Searson

Abstract

Transwell-based models of the blood-brain barrier (BBB) incorporating monolayers of human brain microvascular endothelial cells (dhBMECs) derived from induced pluripotent stem cells show many of the key features of the BBB, including expression of transporters and efflux pumps, expression of tight junction proteins, and physiological values of transendothelial electrical resistance. The fabrication of 3D BBB models using dhBMECs has so far been unsuccessful due to the poor adhesion and survival of these cells on matrix materials commonly used in tissue engineering. To address this issue, we systematically screened a wide range of matrix materials (collagen I, hyaluronic acid, and fibrin), compositions (laminin/entactin), protein coatings (fibronectin, laminin, collagen IV, perlecan, and agrin), and soluble factors (ROCK inhibitor and cyclic adenosine monophosphate) in 2D culture to assess cell adhesion, spreading, and barrier function. Cell coverage increased with stiffness of collagen I gels coated with collagen IV and fibronectin. On 7 mg mL-1 collagen I gels coated with basement membrane proteins (fibronectin, collagen IV, and laminin), cell coverage was high but did not reliably reach confluence. The transendothelial electr...Continue Reading

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Citations

Aug 7, 2019·Expert Opinion on Drug Discovery·Lino Ferreira
Jul 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dominique Thuringer, Carmen Garrido
Feb 25, 2020·Current Pharmaceutical Design·Yoichi Morofuji, Shinsuke Nakagawa
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Apr 24, 2020·Fluids and Barriers of the CNS·Michael J Workman, Clive N Svendsen
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Dec 6, 2018·Fluids and Barriers of the CNS·Jackson G DeStefanoPeter C Searson
Aug 10, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Raleigh M LinvillePeter C Searson
Feb 6, 2019·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Nov 27, 2019·Biomicrofluidics·Pedram MotallebnejadSamira M Azarin
Sep 22, 2020·Current Protocols in Stem Cell Biology·Antje Appelt-MenzelOle Pless
Jul 17, 2020·Microvascular Research·Raleigh M LinvillePeter C Searson
Jan 18, 2019·The American Journal of Pathology·Sae JangAlejandro Soto-Gutierrez
May 1, 2021·Micromachines·Tiffany CameronKaren C Cheung
Jul 14, 2021·Annual Review of Biomedical Engineering·Cynthia HajalBen M Maoz

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Methods Mentioned

BETA
confocal microscopy
AFM

Software Mentioned

ImageJ
Image J
NIS Advanced Research

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