Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

In: Frontiers in Cellular Neuroscience, Vol. 14, 108, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Petersen, N, Torz, L, Jensen, KHR, Hjortø, GM, Spiess, K & Rosenkilde, MM 2020, 'Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium', Frontiers in Cellular Neuroscience, vol. 14, 108. https://doi.org/10.3389/fncel.2020.00108

APA

Petersen, N., Torz, L., Jensen, K. H. R., Hjortø, G. M., Spiess, K., & Rosenkilde, M. M. (2020). Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium. Frontiers in Cellular Neuroscience, 14, [108]. https://doi.org/10.3389/fncel.2020.00108

Vancouver

Petersen N, Torz L, Jensen KHR, Hjortø GM, Spiess K, Rosenkilde MM. Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium. Frontiers in Cellular Neuroscience. 2020;14. 108. https://doi.org/10.3389/fncel.2020.00108

Author

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. In: Frontiers in Cellular Neuroscience. 2020 ; Vol. 14.

Bibtex

@article{510bd0d124c8438b95d23ea32e840d7b,
title = "Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium",
abstract = "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.",
keywords = "blood-cerebrospinal fluid barrier, choroid plexus, epithelium, explant, immune cells, in vitro model, organoid, tight junction markers",
author = "Natalia Petersen and Lola Torz and Jensen, {Kristian H.Reveles} and Hjort{\o}, {Gertrud Malene} and Katja Spiess and Rosenkilde, {Mette Marie}",
year = "2020",
doi = "10.3389/fncel.2020.00108",
language = "English",
volume = "14",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium

AU - Petersen, Natalia

AU - Torz, Lola

AU - Jensen, Kristian H.Reveles

AU - Hjortø, Gertrud Malene

AU - Spiess, Katja

AU - Rosenkilde, Mette Marie

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - blood-cerebrospinal fluid barrier

KW - choroid plexus

KW - epithelium

KW - explant

KW - immune cells

KW - in vitro model

KW - organoid

KW - tight junction markers

U2 - 10.3389/fncel.2020.00108

DO - 10.3389/fncel.2020.00108

M3 - Journal article

C2 - 32431599

AN - SCOPUS:85085144954

VL - 14

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

M1 - 108

ER -

ID: 244570073