Usefulness and limitation of primary cultured porcine choroid plexus epithelial cells as an in vitro model to study drug transport at the blood-CSF barrier.
The epithelial cells of the choroid plexus form the anatomical structure responsible for the blood-cerebrospinal fluid (CSF) barrier. Here we present our recent progress in the application of porcine choroid plexus epithelial cells in the investigation of permeability and transport properties of this tissue in vitro. Isolated cells are seeded on permeable supports where they grow to confluent monolayers. The cell differentiation is significantly increased under serum-free culture conditions, verifiable by an improvement of barrier properties and enhanced characteristics of the epithelial phenotype. We underline the importance of a tight model system for the investigation of transport processes by showing that permeability and transport properties critically depend on the electrical tightness of the monolayer. The mechanisms of vectorial transfer of micronutrients across the epithelial layer have been investigated in detail for ascorbic acid and myo-inositol transport. Additionally, we describe the transfer of organic anions and the expression of the corresponding transport proteins in vitro. The model system was applied to determine permeation rates of various drugs into the CSF. In conclusion our porcine in vitro model of the blood-CSF barrier provides a reliable system to study the transport characteristics of the choroid plexus epithelium and to probe the passage of drugs.
Angelow
Susanne
S
Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, 48149 Münster, Germany.
Zeni
Patrick
P
Galla
Hans-Joachim
HJ
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D013552:Swine; D019108:Tight Junctions / Q000502:physiology