Category: Assay Development and Screening
The blood-brain barrier (BBB) ensures a homeostatic environment for the brain and is made up of specialized endothelial cells and supporting astrocytes and pericytes. The BBB protects the brain from harmful substances. It also prevents large lipophilic compounds, including most therapeutic drugs, from entering the brain. This makes it difficult to treat brain diseases.
While recent developments in microfluidic engineering have resulted in promising in vitro models of the BBB, the throughput and ease of use of these systems is low. This makes these models not suited for regular academic research and drug development. Here, we present a novel BBB model using the 3-lane OrganoPlate®. This platform is based on a 384-well microtiter plate and allows for parallel culture of 40 perfused miniaturized tissues, making it fully compatible with standard lab procedures and equipment.
The BBB-on-a-chip model comprises a perfused 3D microvessel of human brain microvascular endothelial cells. Perfusion through the lumen of the vessel is induced without pumps and can be controlled to model mechanical cues. In addition, the microvessel is supported by human astrocytes and pericytes that interact and support the endothelial vessel. The phenotype of the BBB-on-a-chip was characterized using immunofluorescent staining and showed presence of junctional markers VE-cadherin, PECAM-1, Claudin-5, and ZO-1. In addition, we have confirmed barrier function and adopted transporter assays to show functionality of two major BBB transporters, Pgp and GLUT1.
In conclusion, we present a novel human BBB model in an easy to use microfluidic platform. This model can be used for fundamental BBB research, drug development, or studying neurological disorders.
Remko van Vught– Business Development Manager, Mimetas, Leiden, Netherlands
Business Development Manager
Remko van Vught, PhD is the team leader of business development at MIMETAS. He is a biochemist by training and obtained his Master’s degree in Molecular Life Sciences cum laude at the Radboud University Nijmegen (2009). During his studies he worked on the structure-function relation of MRP4/ABCC4 at Radboud Institute for Molecular Life Sciences (Nijmegen, the Netherlands). At Pepscan Therapeutics (Lelystad, the Netherlands) he studied the targeting of LRP5 to increase bone formation in osteoporosis (TALOS, FP7). He received his PhD at the Utrecht University (Netherlands) where he worked on the development of functionalized nanobodies (antibody fragments) for cancer therapy (2014). After his PhD research, he started as Business Developer at MIMETAS and is responsible for all business development and marketing activities.