A Microfluidic In Vitro Three-Dimensional Dynamic Model of the Blood-Brain Barrier to Study the Transmigration of Immune Cells

Megha Meena; Robin Vandormael; Maxime De Laere; Isabel Pintelon; Zwi Berneman; Regan Watts; Nathalie Cools

doi:10.3390/brainsci12101293

A Microfluidic In Vitro Three-Dimensional Dynamic Model of the Blood-Brain Barrier to Study the Transmigration of Immune Cells

Brain Sci. 2022 Sep 25;12(10):1293. doi: 10.3390/brainsci12101293.

Authors

Megha Meena¹, Robin Vandormael², Maxime De Laere³, Isabel Pintelon⁴, Zwi Berneman^{1

3}, Regan Watts², Nathalie Cools^{1

3}

Affiliations

¹ Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
² Department of Product Development, Faculty of Design Sciences, University of Antwerp, 2000 Antwerp, Belgium.
³ Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium.
⁴ Laboratory of Cell Biology and Histology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.

Abstract

To study the biodistribution of new chemical and biological entities, an in vitro model of the blood-brain barrier (BBB) may become an essential tool during early phases of drug discovery. Here, we present a proof-of-concept of an in-house designed three-dimensional BBB biochip designed by us. This three-dimensional dynamic BBB model consists of endothelial cells and astrocytes, co-cultured on opposing sides of a polymer-coated membrane under flow mimicking blood flow. Our results demonstrate a highly effective BBB as evidenced by (i) a 30-fold increase in transendothelial electrical resistance (TEER), (ii) a significantly higher expression of tight junction proteins, and (iii) the low FITC-dextran permeability of our technical solution as compared to a static in vitro BBB model. Importantly, our three-dimensional BBB model effectively expresses P-glycoprotein (Pg-p), a hallmark characteristic for brain-derived endothelial cells. In conclusion, we provide here a complete holistic approach and insight to the whole BBB system, potentially delivering translational significance in the clinical and pharmaceutical arenas.

Keywords: FITC-dextran permeability; P-glycoprotein; TripleB slides; blood–brain barrier; central nervous system; endothelial cells; microfluidic device; transendothelial electrical resistance.

Grants and funding

This work was supported by BOF DOCPRO4 2015 grant no. 31967 of the Special Research Fund (BOF) from the University of Antwerp, Belgium. Further support was provided through the Methusalem Funding Program from the University of Antwerp, and by the Belgian Charcot Foundation.