9 - Tissue culture of brain endothelial cells – induction of blood–brain barrier properties by brain factors

Summary

Introduction

For several reasons researchers have tried for many years to establish a tissue culture model of the blood–brain barrier (BBB). For ethical reasons the amount of animal experiments should be limited to a reasonable number, and a further consideration is that by simplifying an experimental setting, conditions are much easier to standardize. Because a living animal is of course a complicated organism, many researchers support the idea that isolated brain capillary endothelial cells (BCEC) in culture are a suitable model system, which can be brought to standard conditions more easily, but still give valuable information on how the BBB actually works.

A functioning in vitro model of the BBB should display most, if not all, properties of the barrier in living animals. Among these properties are a very high electrical resistance, due to the presence of tight junctions, in other words a very low paracellular permeability for hydrophilic compounds (including ions), expression of BBB-specific marker proteins, and a cellular polar distribution between luminal and abluminal endothelial plasma membranes of these marker proteins, including transporter proteins.

By isolating BCEC and culturing them, these cells keep their endothelial phenotype, still displaying typical properties. They express angiotensin converting enzyme, von Willebrand factor, and internalize acetylated low-density lipoprotein.

Regrettably, BCEC lose BBB-specific features that they possessed in vivo.