Miranda-Azpiazu, P, Panagiotou, S, Jose, G orcid.org/0000-0001-9856-6755 et al. (1 more author) (2018) A novel dynamic multicellular co-culture system for studying individual blood-brain barrier cell types in brain diseases and cytotoxicity testing. Scientific Reports, 8. ISSN 2045-2322
Abstract
Blood brain barrier (BBB) cells play key roles in the physiology and pathology of the central nervous system (CNS). BBB dysfunction is implicated in many neurodegenerative diseases, including Alzheimer’s disease (AD). The BBB consists of capillary endothelial cells, pericytes encircling the endothelium and surrounding astrocytes extending their processes towards it. Although there have been many attempts to develop in vitro BBB models, the complex interaction between these celltypes makes it extremely difficult to determine their individual contribution to neurotoxicity in vivo. Thus, we developed and optimised an in vitro multicellular co-culture model within the Kirkstall Quasi Vivo System. The main aim was to determine the optimal environment to culture human brain primary endothelial cells, pericytes and astrocytes whilst maintaining cellular communication without formation of a barrier in order to assess the contribution of each cell type to the overall response. As a proof of concept for the present system, the effects of amyloid-beta 25-35 peptide (Aβ25-35), a hall mark of AD, were explored. This multicellular system will be a valuable tool for future studies on the specific roles of individual BBB cell type (while making connection with each other through medium) in CNS disorders as well as in cytotoxicity tests.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number BBSRC BB/M013111/1 Innovate UK - KTP fkaTechnology Strategy Board (KTP) Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jun 2018 11:14 |
Last Modified: | 12 Jun 2019 13:45 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/s41598-018-26480-8 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131743 |