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Human pluripotent stem cell–derived brain pericyte–like cells induce blood-brain barrier properties

Matthew J. Stebbins,Benjamin D. Gastfriend,Scott G. Canfield,Ming-Song Lee,D. Richards,Madeline G Faubion,Wan-Ju Li,R. Daneman,Sean P. Palecek,E. Shusta

Published 2018 in Science Advances

ABSTRACT

The authors differentiate human stem cells to brain pericyte–like cells and integrate them into a neurovascular unit model. Brain pericytes play important roles in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system disorders. While human pluripotent stem cells (hPSCs) have been used to model other NVU cell types, including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, hPSC-derived brain pericyte–like cells have not been integrated into these models. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from hPSCs and subsequently differentiated NCSCs to brain pericyte–like cells. These cells closely resembled primary human brain pericytes and self-assembled with endothelial cells. The brain pericyte–like cells induced blood-brain barrier properties in BMECs, including barrier enhancement and reduced transcytosis. Last, brain pericyte–like cells were incorporated with iPSC-derived BMECs, astrocytes, and neurons to form an isogenic human model that should prove useful for the study of the NVU.

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