Direct Contact Blood Brain Barrier Triculture

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Neurological disorders have been steadily increasing over the last several decades. While drug discovery and development efforts to mitigate these diseases have concurrently increased to meet the change in prevalence, clinical translation into marketed products have been hindered. One of the main difficulties in creating this translation is the lack of a model that can predict the ability of new chemical entities to permeate through the brain blood barrier (BBB). Current models suffer from leakiness of the in vitro cellular tight junctions and that leakiness leads researchers to overestimate the amount of drug permeation.

Researchers at Purdue University have developed a model that represents a more restrictive, accurate model of the BBB. This model is a direct contact, triculture model containing astrocytes, pericytes, and the brain microvessel endothelial cells (BMEC) configured in a physiologically similar manner to an in vivo BBB. This method allows for direct contact between the pericytes and the astrocytes and measures the transendothelial electrical resistance (TEER) as an indirect measure of cell tightness. Researchers monitor the TEER until they determine a window in which a triculture would be of utility for permeability studies. This model will offer superior selectivity for screening neuroactive or neurotoxicant agents in vitro and help in the rational selection of candidates for advancement into further clinical studies based on its physiological similarity to the in vivo BBB cellular configuration. This model may also be adopted to select compounds that have a lower potential of eliciting a neurotoxicant effect.

-More accurate model representing the BBB
-Allows materials to permeate through it
-Allows for direct contact between the astrocytes and pericytes

Potential Applications:
-Research & Development
-Drug discovery

Related Publication:

"Design of experiment based optimization of an in vitro direct contact triculture blood brain barrier model for permeability screening"
Pharmacy & Pharmacology International Journal
Volume 9 Issue 4 - 2021
Sep 7, 2017
Utility Patent
United States
Dec 29, 2020

Dec 18, 2020
CON-Gov. Funding
United States

Sep 7, 2016
United States
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