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In Vitro Models of CNS Barriers

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

N Joan Abbott, Siti R. Yusof, Andreas Reichel, Diana E M Dolman, Jane E Preston

Original languageEnglish
Title of host publicationAAPS Advances in the Pharmaceutical Sciences Series
Subtitle of host publicationPhysiological Concepts, Methodologies and Approaches
Editorsde Lange Elizabeth, Margareta Hammarlund-Udenaes, Robert Thorne
Place of PublicationUSA
PublisherSpringer, Cham
Chapter8
Pages211–254
Number of pages44
Volume33
Edition2
ISBN (Electronic)978-3-030-88773-5
ISBN (Print)978-3-030-88772-8
DOIs
Published25 May 2022

Publication series

NameAAPS Advances in the Pharmaceutical Sciences Series
Volume33
ISSN (Print)2210-7371
ISSN (Electronic)2210-738X

Bibliographical note

Funding Information: We are grateful for discussions and comments from many colleagues especially Prof. Maria Deli, Dr. Alex Avdeef, and Prof. Margareta Hammarlund-Udenaes and for redrawing of Fig. 8.1 by Dr. Robert Thorne and for Fig. 8.4 from Dr. Anika Hartz and Dr. Bjoern Bauer. Publisher Copyright: © 2022, American Association of Pharmaceutical Scientists.

King's Authors

Abstract

In vitro models of the blood-brain barrier provide valuable mechanistic information and useful assay systems for drug discovery and delivery. However, it is important to take into account issues including species differences and to what extent features of the in vivo BBB are retained in cell culture. The history and applications of a primary cells, immortalized cell lines, and stem cell-derived BBB models are reviewed, with evaluation of their strengths and weaknesses, in selecting and optimizing a suitable model for particular applications. Understanding of the unstirred water layers gives insights into the “intrinsic permeability” of the membrane, and proteomic and transcriptomic studies have expanded the characterization of the barrier function. Technologies to derive brain endothelium from human stem cells create 3D models of the neurovascular unit, and miniaturize “organ-on-a-chip” flow systems give great promise for the future. All these technologies are crucial to translate BBB research to viable treatment options for patients.

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