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Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood-brain barrier model

Delsing, L; Kallur, T; Zetterberg, H; Hicks, R; Synnergren, J; (2019) Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood-brain barrier model. Fluids and Barriers of the CNS , 16 , Article 27. 10.1186/s12987-019-0147-4. Green open access

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Abstract

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 diferentiation protocols to astroglia use undefned, animal-containing culture matrices. Laminins, which play an essential role in the regulation of cell behavior, ofer a source of defned, animal-free culture matrix. Methods: In order to understand how laminins afect astroglia diferentiation, 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 diferentiated on human LN521 showed higher expression of several astroglia specifc mRNAs and proteins such as GFAP, S100B, Angiopoietin-1, and EAAT1, compared to astroglia diferentiated on murine L2020. In addition, glutamate uptake and ability to induce expression of junction proteins in endothelial cells were afected by the culture matrix for diferentiation. Conclusion: Our results suggest that astroglia diferentiated 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 defned and robust derivation of astroglia for use in BBB coculture models.

Type: Article
Title: Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood-brain barrier model
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12987-019-0147-4
Publisher version: https://doi.org/10.1186/s12987-019-0147-4
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Astroglia, hiPSC, In vitro models, Diferentiation, Laminin-521, Blood–brain barrier
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10081560
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