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

Artikel i vetenskaplig tidskrift
Författare Louise Delsing
Pierre Dönnes
José Sánchez
Maryam Clausen
Dimitrios Voulgaris
Anna Falk
Anna Herland
Gabriella Brolén
Henrik Zetterberg
Ryan Hicks
Jane Synnergren
Publicerad i Stem cells (Dayton, Ohio)
Volym 36
Nummer/häfte 12
Sidor 1816-1827
ISSN 1549-4918
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1816-1827
Språk en
Länkar dx.doi.org/10.1002/stem.2908
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Neurokemi

Sammanfattning

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 barrier formation on a functional and transcriptional level. The information about gene expression changes in coculture can be used to further improve iPSC-derived BBB models through selective pathway manipulation. Stem Cells 2018;36:1816-12.

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