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dc.contributor.authorBergmann, Sonja
dc.contributor.authorLawler, Sean E.
dc.contributor.authorQu, Yuan
dc.contributor.authorFadzen, Colin M.
dc.contributor.authorWolfe, Justin
dc.contributor.authorRegan, Michael S.
dc.contributor.authorPentelute, Bradley L.
dc.contributor.authorAgar, Nathalie Y. R.
dc.contributor.authorCho, Choi-Fong
dc.date.accessioned2020-01-24T16:21:52Z
dc.date.available2020-01-24T16:21:52Z
dc.date.issued2018-10-31
dc.date.submitted2018
dc.identifier.issn1754-2189
dc.identifier.issn1750-2799
dc.identifier.urihttps://hdl.handle.net/1721.1/123679
dc.description.abstractIn vitro models of the blood–brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. ‘BBB organoids’ are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2–3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies. Keywords: biological models; blood–brain barrier; cytological techniques; drug screeningen_US
dc.language.isoen
dc.publisherSpringer Natureen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/s41596-018-0066-xen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleBlood–brain-barrier organoids for investigating the permeability of CNS therapeuticsen_US
dc.typeArticleen_US
dc.identifier.citationBergmann, Sonja et al. "Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics." Nature Protocols 13, 12 (December 2018): 2827–2843 © 2018 Springer Natureen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.relation.journalNature Protocolsen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-01-02T18:05:56Z
dspace.date.submission2020-01-02T18:05:59Z
mit.journal.volume13en_US
mit.journal.issue12en_US


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