Usefulness of a humanized tricellular static transwell blood–brain barrier model as a microphysiological system for drug development applications. - A case study based on the benchmark evaluations of blood-brain barrier microphysiological system

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

“…The pore size and density can vary depending on the application. Usually, between 0.2 and 3 µm pores are used for transport studies and tissue engineering [ 121 , 122 , 123 ]. Thus, interactions between different cell types can be studied in co-culture models while maintaining a physical separation.…”

“…They are suitable for a wide range of applications, but are also more expensive. Coating the membranes with BM components, such as collagen type IV or fibronectin, is recommended for better cell attachments and morphologies [ 123 ]. Recent models used the co-cultures of human immortalized cell lines [ 123 , 125 ], primary cells [ 122 ], or iPSCs [ 126 , 127 , 128 , 129 ].…”

“…Coating the membranes with BM components, such as collagen type IV or fibronectin, is recommended for better cell attachments and morphologies [ 123 ]. Recent models used the co-cultures of human immortalized cell lines [ 123 , 125 ], primary cells [ 122 ], or iPSCs [ 126 , 127 , 128 , 129 ]. Some of them incorporated hydrogels on one side of the insert with glial cells to obtain a more physiologically relevant ECM setup [ 129 , 130 , 131 ].…”

“…Additionally, the markers for efflux transporters, such as P-gp, BCRP, Mrp, or solute carriers can be utilized to ensure BMEC functionality and polarity [ 187 ]. A recent study by Nakayama-Kitamura et al [ 123 ] set up evaluation parameters for the in vitro human BBB likeness that is needed for drug development. The parameters comprised TJ markers (claudin-5 and ZO-1), TEER, the endothelial cell marker CD31, transporters (P-gp, glucose transporter protein-1, and BCRP), and receptor-mediated transcytosis (transferrin receptor).…”

Sensor extended imaging workflow for creating fit for purpose models in basic and applied cell biology

“…Going forward, we can use the increased knowledge to develop next-generation MPS that will allow us to manipulate and observe the cells simultaneously in a biologically relevant context. Most of the parameters mentioned above are included in the different MPS systems with an emphasis on mimicking organ-specific fluidics such as blood–brain barrier 36 , gut 37 , or lung 38 . The plethora of different biological components such as cell source or matrices is accompanied by an even greater spectrum of biomechanical features and sensor modules.…”