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Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood-brain barrier model
Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden / Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Mölndal, Sweden. (Translationell Bioinformatik, Translational Bioinformatics)ORCID-id: 0000-0003-2899-3801
BioLamina, Sundbyberg, Sweden.
Department of Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden / Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK / UK Dementia Research Institute at UCL, London, UK.
Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Mölndal, Sweden.
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2019 (Engelska)Ingår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 16, nr 1, artikel-id 27Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background Human induced pluripotent stem cells (hiPSC) hold great promise for use in cell therapy applications and for improved in vitro models of human disease. So far, most hiPSC differentiation protocols to astroglia use undefined, animal-containing culture matrices. Laminins, which play an essential role in the regulation of cell behavior, offer a source of defined, animal-free culture matrix. Methods In order to understand how laminins affect astroglia differentiation, recombinant human laminin-521 (LN521), was compared to a murine Engelbreth-Holm-Swarm sarcoma derived laminin (L2020). Astroglia expression of protein and mRNA together with glutamate uptake and protein secretion function, were evaluated. Finally, these astroglia were evaluated in a coculture model of the blood-brain barrier (BBB). Results Astroglia of good quality were generated from hiPSC on both LN521 and L2020. However, astroglia differentiated on human LN521 showed higher expression of several astroglia specific mRNAs and proteins such as GFAP, S100B, Angiopoietin-1, and EAAT1, compared to astroglia differentiated on murine L2020. In addition, glutamate uptake and ability to induce expression of junction proteins in endothelial cells were affected by the culture matrix for differentiation. Conclusion Our results suggest that astroglia differentiated on LN521 display an improved phenotype and are suitable for coculture in a hiPSC-derived BBB model. This provides a starting point for a more defined and robust derivation of astroglia for use in BBB coculture models.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2019. Vol. 16, nr 1, artikel-id 27
Nyckelord [en]
Astroglia, hiPSC, In vitro models, Diferentiation, Laminin-521, Blood–brain barrier
Nationell ämneskategori
Farmaceutiska vetenskaper
Forskningsämne
Bioinformatik
Identifikatorer
URN: urn:nbn:se:his:diva-17672DOI: 10.1186/s12987-019-0147-4ISI: 000483547700001PubMedID: 31462266Scopus ID: 2-s2.0-85071630761OAI: oai:DiVA.org:his-17672DiVA, id: diva2:1350718
Tillgänglig från: 2019-09-12 Skapad: 2019-09-12 Senast uppdaterad: 2019-11-13Bibliografiskt granskad

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Delsing, LouiseSynnergren, Jane

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