Abstract
Stem Cell Reports 2019, 12, 474-487
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
There is a profound need for functional, biomimetic in vitro聽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聽(iPSC)-derived human brain聽microvascular endothelial cells聽(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鈥�100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell聽and human dermal microvascular endothelial cell聽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聽model of the human NVU constructed from iPSCs.