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Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics

Author(s)
Bergmann, Sonja; Lawler, Sean E.; Qu, Yuan; Fadzen, Colin M.; Wolfe, Justin; Regan, Michael S.; Pentelute, Bradley L.; Agar, Nathalie Y. R.; Cho, Choi-Fong; ... Show more Show less
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Abstract
In 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 screening
Date issued
2018-10-31
URI
https://hdl.handle.net/1721.1/123679
Department
Massachusetts Institute of Technology. Department of Chemistry
Journal
Nature Protocols
Publisher
Springer Nature
Citation
Bergmann, Sonja et al. "Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics." Nature Protocols 13, 12 (December 2018): 2827–2843 © 2018 Springer Nature
Version: Author's final manuscript
ISSN
1754-2189
1750-2799

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