RT Journal Article
SR Electronic
T1 Human pluripotent stem cell-derived brain pericyte-like cells induce blood-brain barrier properties
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 387100
DO 10.1101/387100
A1 Matthew J. Stebbins
A1 Benjamin D. Gastfriend
A1 Scott G. Canfield
A1 Ming-Song Lee
A1 Drew Richards
A1 Madeline G. Faubion
A1 Wan-Ju Li
A1 Richard Daneman
A1 Sean P. Palecek
A1 Eric V. Shusta
YR 2018
UL http://biorxiv.org/content/early/2018/08/07/387100.abstract
AB Brain pericytes play an important role in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system (CNS) disorders. While human pluripotent stem cells (hPSCs) have been used to model other components of the NVU including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, cells having brain pericyte-like phenotypes have not been described. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from human pluripotent stem cells (hPSCs) and subsequently differentiated NCSCs to brain pericyte-like cells. The brain pericyte-like cells expressed marker profiles that closely resembled primary human brain pericytes, and they self-assembled with endothelial cells to support vascular tube formation. Importantly, the brain pericyte-like cells induced blood-brain barrier (BBB) properties in BMECs, including barrier enhancement and reduction of transcytosis. Finally, brain pericyte-like cells were incorporated with iPSC-derived BMECs, astrocytes, and neurons to form an isogenic human NVU model that should prove useful for the study of the BBB in CNS health, disease, and therapy.AbbreviationsBBBblood-brain barrierBMECsbrain microvascular endothelial cellsCNScentral nervous systemE6-CSFDE6 medium supplemented with CHIR99021, SB431542, FGF2, and dorsomorphinEGM-2endothelial growth factor medium 2hESCshuman embryonic stem cellshPSCshuman pluripotent stem cellsiPSCsinduced pluripotent stem cellsNCSCneural crest stem cellsNVUneurovascular unitvSMCsvascular smooth muscle cells