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Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium

The choroid plexus (CP) plays a major role in controlling the entry of substances and immune cells into the brain as it forms the blood-cerebrospinal fluid barrier (BCSFB) in the brain ventricles. Dysregulated immune cell trafficking through the epithelial cell (EC) layer of CP is central for the pa...

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Autores principales: Petersen, Natalia, Torz, Lola, Jensen, Kristian H. Reveles, Hjortø, Gertrud Malene, Spiess, Katja, Rosenkilde, Mette Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214744/
https://www.ncbi.nlm.nih.gov/pubmed/32431599
http://dx.doi.org/10.3389/fncel.2020.00108
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author Petersen, Natalia
Torz, Lola
Jensen, Kristian H. Reveles
Hjortø, Gertrud Malene
Spiess, Katja
Rosenkilde, Mette Marie
author_facet Petersen, Natalia
Torz, Lola
Jensen, Kristian H. Reveles
Hjortø, Gertrud Malene
Spiess, Katja
Rosenkilde, Mette Marie
author_sort Petersen, Natalia
collection PubMed
description The choroid plexus (CP) plays a major role in controlling the entry of substances and immune cells into the brain as it forms the blood-cerebrospinal fluid barrier (BCSFB) in the brain ventricles. Dysregulated immune cell trafficking through the epithelial cell (EC) layer of CP is central for the pathogenesis of infectious diseases in the brain and many neurodegenerative disorders. In vitro studies elucidating the function of the CP have so far been limited to the monolayer culture of CP ECs. To mimic immune cell migration across the CP barrier, a three-dimensional model would be advantageous. Here, we present an in vitro platform for studies of the immune cell trafficking based on CP explants/organoids. The explants were generated from fragments of mouse CPs in Matrigel, where the cells formed luminal spaces and could be maintained in culture for at least 8 weeks. We demonstrate expression of the major CP markers in the explants, including transthyretin and aquaporin 1 as well as ZO1 and ICAM-1, indicating a capacity for secretion of cerebrospinal fluid (CSF) and presence of tight junctions. CP explants displayed CP-like cell polarization and formed an intact EC barrier. We also show that the expression of transthyretin, transferrin, occludin and other genes associated with various functions of CP was maintained in the explants at similar levels as in native CP. By using dendritic cells and neutrophils, we show that the migration activity of immune cells and their interactions with CP epithelium can be monitored by microscopy. Thereby, the three-dimensional CP explant model can be used to study the cellular and molecular mechanisms mediating immune cell migration through CP epithelium and other functions of choroid EC. We propose this platform can potentially be used in the search for therapeutic targets and intervention strategies to improve control of (drug) substances and (immune) cell entry into the central nervous system.
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spelling pubmed-72147442020-05-19 Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium Petersen, Natalia Torz, Lola Jensen, Kristian H. Reveles Hjortø, Gertrud Malene Spiess, Katja Rosenkilde, Mette Marie Front Cell Neurosci Cellular Neuroscience The choroid plexus (CP) plays a major role in controlling the entry of substances and immune cells into the brain as it forms the blood-cerebrospinal fluid barrier (BCSFB) in the brain ventricles. Dysregulated immune cell trafficking through the epithelial cell (EC) layer of CP is central for the pathogenesis of infectious diseases in the brain and many neurodegenerative disorders. In vitro studies elucidating the function of the CP have so far been limited to the monolayer culture of CP ECs. To mimic immune cell migration across the CP barrier, a three-dimensional model would be advantageous. Here, we present an in vitro platform for studies of the immune cell trafficking based on CP explants/organoids. The explants were generated from fragments of mouse CPs in Matrigel, where the cells formed luminal spaces and could be maintained in culture for at least 8 weeks. We demonstrate expression of the major CP markers in the explants, including transthyretin and aquaporin 1 as well as ZO1 and ICAM-1, indicating a capacity for secretion of cerebrospinal fluid (CSF) and presence of tight junctions. CP explants displayed CP-like cell polarization and formed an intact EC barrier. We also show that the expression of transthyretin, transferrin, occludin and other genes associated with various functions of CP was maintained in the explants at similar levels as in native CP. By using dendritic cells and neutrophils, we show that the migration activity of immune cells and their interactions with CP epithelium can be monitored by microscopy. Thereby, the three-dimensional CP explant model can be used to study the cellular and molecular mechanisms mediating immune cell migration through CP epithelium and other functions of choroid EC. We propose this platform can potentially be used in the search for therapeutic targets and intervention strategies to improve control of (drug) substances and (immune) cell entry into the central nervous system. Frontiers Media S.A. 2020-05-05 /pmc/articles/PMC7214744/ /pubmed/32431599 http://dx.doi.org/10.3389/fncel.2020.00108 Text en Copyright © 2020 Petersen, Torz, Jensen, Hjortø, Spiess and Rosenkilde. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Petersen, Natalia
Torz, Lola
Jensen, Kristian H. Reveles
Hjortø, Gertrud Malene
Spiess, Katja
Rosenkilde, Mette Marie
Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title_full Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title_fullStr Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title_full_unstemmed Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title_short Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium
title_sort three-dimensional explant platform for studies on choroid plexus epithelium
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214744/
https://www.ncbi.nlm.nih.gov/pubmed/32431599
http://dx.doi.org/10.3389/fncel.2020.00108
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