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

Natalia Petersen1, Lola Torz2, Kristian H Reveles Jensen2

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Frontiers in Cellular Neuroscience
|May 21, 2020
PubMed
Summary

Researchers developed a 3D in vitro model using choroid plexus (CP) explants to study immune cell trafficking across the blood-cerebrospinal fluid barrier (BCSFB). This novel platform allows for better understanding of brain entry mechanisms for immune cells and substances.

Keywords:
blood-cerebrospinal fluid barrierchoroid plexusepitheliumexplantimmune cellsin vitro modelorganoidtight junction markers

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • The choroid plexus (CP) forms the blood-cerebrospinal fluid barrier (BCSFB), crucial for regulating brain entry.
  • Dysregulated immune cell trafficking across the CP is implicated in brain infections and neurodegenerative diseases.
  • Current in vitro models using CP epithelial cell monolayers do not fully replicate the CP's complex 3D structure.

Purpose of the Study:

  • To develop and validate a novel 3D in vitro platform for studying immune cell migration across the CP.
  • To investigate the cellular and molecular mechanisms of immune cell trafficking at the BCSFB.
  • To provide a tool for identifying therapeutic targets to control substance and immune cell entry into the central nervous system.

Main Methods:

  • Generation of 3D choroid plexus explants from mouse CPs embedded in Matrigel.
  • Culture and maintenance of explants for up to 8 weeks.
  • Assessment of CP marker expression (transthyretin, aquaporin 1, ZO1, ICAM-1, transferrin, occludin) via microscopy and gene expression analysis.
  • Monitoring of immune cell (dendritic cells, neutrophils) migration and interaction with CP epithelium using microscopy.

Main Results:

  • CP explants successfully formed luminal spaces, maintained CP marker expression, and exhibited CP-like cell polarization and an intact epithelial barrier.
  • The explants preserved the expression of key genes associated with CP function, similar to native CP.
  • The 3D model allowed for the visualization and study of immune cell migration and interaction with the CP epithelium.

Conclusions:

  • The 3D choroid plexus explant model effectively mimics the native BCSFB structure and function in vitro.
  • This platform is suitable for studying immune cell trafficking and interactions at the CP epithelium.
  • The model offers a promising tool for developing therapeutic strategies to modulate substance and immune cell entry into the brain.