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Monday, October 21 • 3:45pm - 3:55pm
Lost in Translation: Success through Collaboration- A Scalable iPSC-Derived Blood Brain Barrier Penetration Assay in Perfused Endothelial Micro-Tubes to Test Anti-Inflammatory Drugs

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The human blood–brain barrier (BBB) is a protective and regulatory interface that permits entry of essential nutrients, while preventing harmful substances from entering the central nervous system (CNS). From the pharmacological perspective, the BBB is one of the major hurdles of CNS drug delivery. Recent BBB models based on human iPSC-derived brain microvascular endothelial cells (BMECs) provide optimal BBB properties and scalability for brain-penetration tests in early drug discovery. However, advanced BMEC differentiation protocols require expensive co-cultures of primary cells to improve the BBB phenotype and thereby hamper the upscaling of a screen. Here we present a contemporary, cost effective and scalable BMEC differentiation method for brain-penetration tests with primary cell-conditioned media that provide similar barrier properties compared to co-culture methods. In a pilot study, a collection of anti-inflammatory compounds have been tested for brain-penetration compared to reference substances. After confirming the integrity of the endothelial barrier, the concentrations of each permeated compound was measured. Supernatants containing passed compounds were finally used to quantify their anti-inflammatory effect in a cytokine-release assay based on human immune cells. In summary, toxicity, penetrability, and anti-inflammatory functionality were determined for each compound. Finally, our method was miniaturized on a filter-free organ-on-a-chip platform allowing tube-like formation of matured BMECs in a perfused microfluidic device which reflects in vivo BBB physiology even better. 

Speakers
avatar for Sven Fengler, Ph.D.

Sven Fengler, Ph.D.

PostDoc, DZNE Bonn Germany
2017 - current, PostDoc Laboratory Automation Technologies (LAT) – Core Research Facilities & Services, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany 2015 - 2017, PostDoc Department of Molecular Biology I, Centre for Medical Biotechnology (ZMB) University Essen... Read More →

Chair

Monday October 21, 2019 3:45pm - 3:55pm
Wellcome Auditorium