090. Choroid plexus-on-a-chip: A microfluidic in vitro model to study the effect of inflammation on the blood-cerebrospinal fluid barrier

Authors: Carolyn Harris

A monolayer of choroid plexus epithelial cells (CPECs) surrounding a core of fenestrated capillaries together constitute the blood-cerebrospinal fluid barrier (BCSFB). This tissue, located in the ventricles of the brain, is responsible for a majority of cerebrospinal fluid (CSF) production, regulation of molecules into the brain, and neuro-immune surveillance. Transwell plates and explant cultures have become important in vitro tools to study how these functions are altered in pathologic conditions like hydrocephalus.Methods: We built on these existing models and leveraged microfluidic techniques to develop a 2-channel barrier-on-a-chip device that recapitulates the dynamic environment of the BCSFB. The choroid plexus-on-a-chip was designed with channel dimensions informed by computational fluid dynamics and fabricated using 3D printing and soft lithography techniques. Briefly, a porous polyethylene terephthalate membrane was sandwiched between two pieces of polydimethylsiloxane, forming the luminal and abluminal compartments. CPECs grown in the abluminal compartment establish a tightly connected, low permeability monolayer. Syringe pumps were used to provide the mechanical cue of hemodynamic shear stress from the luminal side and low ventricular wall shear from the abluminal side.
In this way, changes in the monolayer’s integrity can be tracked by quantifying FITC-Dextran leakage across the compartments. Additionally, a four-electrode setup incorporated into the chip can be used to record trans epithelial electrical resistance as a measure of barrier function.
Future work involves inflicting chemical injury to the BCSFB and testing hypotheses surrounding inflammation mediated BCSFB dysfunction in hydrocephalus.