Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies

Park, Tae‐Eun; Mustafaoğlu, Nur; Herland, Anna; Hasselkus, Ryan; Mannix, Robert; Fitzgerald, Edward A.; Prantil‐Baun, Rachelle; Watters, Alexander L.; Henry, Olivier; Benz, Maximilian A.; Sanchez, Henry; McCrea, Heather J.; Goumnerova, Liliana; Song, Hannah; Palecek, Sean P.; Shusta, Eric V.; Ingber, Donald E.

doi:10.1038/s41467-019-10588-0

articleNature CommunicationsJun 13, 2019GOLD OA

Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies

TPTae‐Eun Park NMNur Mustafaoğlu AHAnna Herland RHRyan Hasselkus RMRobert Mannix

Harvard University · Ulsan National Institute of Science and Technology · +7 more institutions

PubMed

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Abstract

The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was…

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Topics & keywords

Topics

Keywords

Blood–brain barrier
Transcytosis
In vivo
Cell biology
In vitro
Organ-on-a-chip
Tight junction
Human brain

UN Sustainable Development Goals

Good health and well-being

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