Title:Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders
Volume: 15
Issue: 3
Author(s): Alexander L. Rusanov, Natalia G. Luzgina, George E. Barreto and Gjumrakch Aliev
Affiliation:
Keywords:
Blood-brain barrier; in vitro cell models; transport; permeability; drug development; shear stress; microfluidics;
endothelial cells.
Abstract: In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical
evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we
summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare
analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the
BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these
conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions,
including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of
transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the
accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of
different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the
mutual influences of cells under normal conditions and when exposed to the test substance. New experimental
possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in
the practice for pre-clinical studies of novel drugs against neurodegenerative diseases.
