iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds.

Faley SL, Neal EH, Wang JX, Bosworth AM, Weber CM, Balotin KM, Lippmann ES, Bellan LM
Stem Cell Reports. 2019 12 (3): 474-487

PMID: 30773484 · PMCID: PMC6409430 · DOI:10.1016/j.stemcr.2019.01.009

There is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases and identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (BMECs) exhibit robust barrier functionality when cultured in 3D channels within gelatin hydrogels. We determined that BMECs cultured in 3D under perfusion conditions were 10-100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell and human dermal microvascular endothelial cell controls, and the BMECs maintained barrier function for up to 21 days. Analysis of cell-cell junctions revealed expression patterns supporting barrier formation. Finally, efflux transporter activity was maintained over 3 weeks of perfused culture. Taken together, this work lays the foundation for development of a representative 3D in vitro model of the human NVU constructed from iPSCs.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (12)

Albumins Blood-Brain Barrier Brain Cells, Cultured Dextrans Endothelial Cells Endothelium Fluorescein Humans Hydrogels Induced Pluripotent Stem Cells Microvessels

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