Barrier Properties and Transcriptome Expression in Human iPSC-Derived Models of the Blood-Brain Barrier

Stem Cells
Louise DelsingJane Synnergren

Abstract

Cell-based models of the blood-brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in coculture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our coculture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in coculture, including upregulation of tight junction proteins, such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF, and PI3K-Akt pathways upon coculture. Our data suggest that coculture of iPSC-derived endothelial cells promotes ba...Continue Reading

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Citations

Aug 30, 2019·Fluids and Barriers of the CNS·Louise DelsingJane Synnergren
Feb 6, 2019·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Jun 24, 2020·Tissue Engineering. Part B, Reviews·Richard JeskeYan Li
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Apr 24, 2020·Fluids and Barriers of the CNS·Michael J Workman, Clive N Svendsen
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Oct 21, 2020·Fluids and Barriers of the CNS·Ethan S LippmannEric V Shusta
Feb 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Tyler M LuRaphaël Lis
Feb 26, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sara WellensMaxime Culot
Jul 28, 2020·Molecular and Cellular Neurosciences·Louise DelsingHenrik Zetterberg
Mar 25, 2021·APL Bioengineering·Callie M Weber, Alisa Morss Clyne
Apr 20, 2021·Frontiers in Physiology·Tyler M LuRaphaël Lis
Jun 4, 2021·Cell Stem Cell·Jane NguyenSharon Gerecht
Jul 25, 2021·International Journal of Molecular Sciences·Ying-Chieh WuŠárka Lehtonen
Oct 26, 2021·Journal of Pharmaceutical Sciences·Saba HammadRania Harati

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