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

Nature communications, 2019-06, Vol.10 (1), p.2621-12, Article 2621 [Peer Reviewed Journal]

2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2019 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-019-10588-0 ;PMID: 31197168

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Title:
Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies
Author: Park, Tae-Eun ; Mustafaoglu, Nur ; Herland, Anna ; Hasselkus, Ryan ; Mannix, Robert ; FitzGerald, Edward A ; Prantil-Baun, Rachelle ; Watters, Alexander ; Henry, Olivier ; Benz, Maximilian ; Sanchez, Henry ; McCrea, Heather J ; Goumnerova, Liliana Christova ; Song, Hannah W ; Palecek, Sean P ; Shusta, Eric ; Ingber, Donald E
Subjects: Antibodies ; Antibodies - pharmacology ; Astrocytes ; Biochips ; Blood-brain barrier ; Blood-Brain Barrier - cytology ; Blood-Brain Barrier - metabolism ; Brain ; Brain stem ; Cell culture ; Central nervous system ; Drug delivery ; Drug delivery systems ; Drug Delivery Systems - methods ; Drug development ; Drug Evaluation, Preclinical - instrumentation ; Drug Evaluation, Preclinical - methods ; Drugs ; Efflux ; Endothelial Cells - metabolism ; Endothelium ; Endothelium, Vascular - cytology ; Humans ; Hypoxia ; Immunoglobulins ; Lab-On-A-Chip Devices ; Medicin och hälsovetenskap ; Microfluidics ; Microfluidics - instrumentation ; Microfluidics - methods ; Microvasculature ; Microvessels - cytology ; Peptides ; Pericytes ; Permeability ; Pluripotency ; Pluripotent Stem Cells ; Primary Cell Culture - instrumentation ; Primary Cell Culture - methods ; Selectivity ; Stem cells
Is Part Of: Nature communications, 2019-06, Vol.10 (1), p.2621-12, Article 2621
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-019-10588-0
PMID: 31197168
Source: MEDLINE
PubMed Central
SWEPUB Freely available online
ProQuest Central
DOAJ Directory of Open Access Journals

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

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