his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. 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.
Biostatistics, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
Show others and affiliations
2018 (English)In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 36, no 12, p. 1816-1827Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2018. Vol. 36, no 12, p. 1816-1827
Keywords [en]
blood–brain barrier, co-culture, hiPSC, in vitro models, transcriptome, endothelial cells
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Bioinformatics; INF502 Biomarkers
Identifiers
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
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-08-23Bibliographically approved

Open Access in DiVA

fulltext(1218 kB)34 downloads
File information
File name FULLTEXT03.pdfFile size 1218 kBChecksum SHA-512
f4492cddd8ee07b8bac9764f9cbdf998aa803f0859ec009468521524aceced421934d8949bcf55b8cfd36cd4c2644823f7f7fdeb62e8a0a5b13323acc8cef21b
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records BETA

Delsing, LouiseSynnergren, Jane

Search in DiVA

By author/editor
Delsing, LouiseSynnergren, Jane
By organisation
School of BioscienceThe Systems Biology Research Centre
In the same journal
Stem Cells
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
Total: 36 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 213 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf