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Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;UNIST, UNIST Gil 50, Ulsan 44919, South Korea..
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems. Harvard Univ, USA ;Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, Stockholm, Sweden..
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 2621Article in journal (Refereed) Published
Abstract [en]

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 accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 10, article id 2621
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Nano Technology
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URN: urn:nbn:se:kth:diva-254498DOI: 10.1038/s41467-019-10588-0ISI: 000471227300024PubMedID: 31197168OAI: oai:DiVA.org:kth-254498DiVA, id: diva2:1337512
Note

QC 20190715

Available from: 2019-07-15 Created: 2019-07-15 Last updated: 2019-07-15Bibliographically approved

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