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Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier
Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Institute of Neuroscience and Physiology, Gothenburg, Sweden / Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden. (Bioinformatik, Bioinformatics)ORCID-id: 0000-0003-2899-3801
SciCross AB, Skövde, Sweden.ORCID-id: 0000-0002-4613-2952
Biostatistics, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
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2018 (Engelska)Ingår i: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 36, nr 12, s. 1816-1827Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 inter-species 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 co-culture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our co-culture 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 co-culture, 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 co-culture. Our data suggests that co-culture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in co-culture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.

Ort, förlag, år, upplaga, sidor
AlphaMed Press, Inc. , 2018. Vol. 36, nr 12, s. 1816-1827
Nyckelord [en]
blood–brain barrier, co-culture, hiPSC, in vitro models, transcriptome, endothelial cells
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
Bioinformatik; INF502 Biomarkörer
Identifikatorer
URN: urn:nbn:se:his:diva-16283DOI: 10.1002/stem.2908ISI: 000455838500004PubMedID: 30171748Scopus ID: 2-s2.0-85056115357OAI: oai:DiVA.org:his-16283DiVA, id: diva2:1254133
Tillgänglig från: 2018-10-08 Skapad: 2018-10-08 Senast uppdaterad: 2019-11-19Bibliografiskt granskad

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Delsing, LouiseDönnes, PierreSynnergren, Jane

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Delsing, LouiseDönnes, PierreSynnergren, Jane
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Institutionen för biovetenskapForskningscentrum för Systembiologi
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Stem Cells
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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