Cell Interplay Model to Assess the Impact of Glioma Cells on Blood-Brain Barrier Permeability.

Abstract

The blood-brain barrier (BBB) is the most selective protecting layer of the central nervous system (CNS) with unique neurovascular features. The BBB is known to undergo a process of molecular alterations during disease state, such as in the case of glioma. This results in a non-uniform permeability along the BBB layer, which retains intact regions but develops focal sites of higher leakiness, especially in the surrounds of the tumor core. Although essential to guarantee brain homeostasis, the BBB has been the Achilles heel of drug delivery to the brain since the early times of the first classification as "barrier," more than a century ago. Due to the presence of the BBB, the transport of drug molecules from the bloodstream to the brain parenchyma is highly restricted, and, therefore, clinically relevant therapeutic concentrations cannot be achieved. Research efforts have focused on the development of novel tools to ameliorate drug permeability across the BBB, including drug formulation into non-invasive delivery systems with brain targeting properties and techniques that allow a temporary disruption of the BBB. To strengthen the advancement of potential drug candidates, in vitro models that recapitulate the main in vivo features of BBB are required to perform a preliminary screening of permeability, both in health and disease conditions. Herein, a protocol to assemble a BBB in vitro model to screen drug permeability in a glioma disease state is detailed. The model consists of a BBB and glioma cell co-culture and aims at exploiting the effect of the interplay between the cell constituents on the permeability of drug molecules. Although simple and straightforward, the herein in vitro model presents a high reproducibility, cost-effectiveness, and a favorable time-benefit balance.