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Barrier properties ...
Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier
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- Delsing, Louise (author)
- Gothenburg University,Göteborgs universitet,Högskolan i Skövde,Institutionen för biovetenskap,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,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Dönnes, Pierre (author)
- SciCross AB, Skövde, Sweden
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- Sánchez, José (author)
- Biostatistics, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden
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- Clausen, Maryam (author)
- Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden
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- Voulgaris, Dimitrios, 1990- (author)
- KTH,Mikro- och nanosystemteknik,Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden
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- Falk, Anna (author)
- Karolinska Institutet
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- Herland, Anna (author)
- Karolinska Institutet,KTH,Mikro- och nanosystemteknik,Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden / Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Brolén, Gabriella (author)
- Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Hicks, Ryan (author)
- Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden
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- Synnergren, Jane (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Bioinformatik, Bioinformatics
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(creator_code:org_t)
- 2018-11-05
- 2018
- English.
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In: Stem Cells. - : AlphaMed Press, Inc.. - 1066-5099 .- 1549-4918. ; 36:12, s. 1816-1827
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- blood–brain barrier
- co-culture
- hiPSC
- in vitro models
- transcriptome
- endothelial cells
- Bioinformatik
- Bioinformatics
- INF502 Biomarkers
- INF502 Biomarkörer
Publication and Content Type
- ref (subject category)
- art (subject category)
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Stem Cells
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To the university's database
- By the author/editor
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Delsing, Louise
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Dönnes, Pierre
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Sánchez, José
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Clausen, Maryam
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Voulgaris, Dimit ...
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Falk, Anna
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show more...
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Herland, Anna
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Brolén, Gabriell ...
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Zetterberg, Henr ...
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Hicks, Ryan
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Synnergren, Jane
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Stem Cells
- By the university
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University of Skövde
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Royal Institute of Technology
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Karolinska Institutet
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University of Gothenburg