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

• DOI: 10.1016/j.stemcr.2019.01.009
• Publication Date: 2019-02-14T15:42:39Z
• Authors: Shannon L. Faley; Emma H. Neal; Jason X. Wang; Allison M. Bosworth; Callie M. Weber; Kylie M. Balotin; Ethan S. Lippmann; Leon M. Bellan
• Keywords: Barrier function

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 identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) exhibit robust functionality when cultured 3D channels within gelatin hydrogels. We determined BMECs under perfusion conditions were 10-100 times less permeable sodium fluorescein, 3 kDa dextran, albumin relative umbilical vein dermal controls, maintained function up 21 days. Analysis cell-cell junctions revealed expression patterns supporting formation. Finally, efflux transporter activity was over weeks perfused culture. Taken together, this work lays foundation development representative NVU constructed from iPSCs.