Journal
STEM CELL REPORTS
Volume 12, Issue 3, Pages 474-487Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2019.01.009
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Funding
- NIBIB [NIH 4R00EB013630]
- NSF [BMAT 1506717, CBET 1706155]
- NARSAD Young Investigator Award from the Brain and Behavior Research Foundation
- Alzheimer's Disease Research, a program of the BrightFocus Foundation [A20170945]
- National Science Foundation Graduate Research Fellowship
- SyBBURE Searle Undergraduate Research Program
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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.
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