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DMDG 2024
The 50th DMDG Open Meeting will take place at Heslington Campus East, University of York, September 2nd-4th, 2024. The meeting will spend some time looking back at 50 years of Open Meetings and the contributions made by the DMDG to ADME/DMPK science of 5 decades in addition to looking forward to the next 50 years of contribution.
Thank you for visiting us at DMDG!
Our dedicated team will be available to answer questions and share over a decade of organ-on-a-chip (OOC) expertise with you at DMDG 2024!
We look forward to introducing you to our PhysioMimix® suite of hardware, consumables, assay protocols and contract research services. Discover how our solutions deliver clinically relevant mechanistic data that enable you to design cost-efficient in vivo studies (using fewer animals) and improve your ability to predict clinical outcomes.
Plus, meet the new game-changing product in our PhysioMimix OOC range of microphysiological systems, the PhysioMimix Single-organ Higher Throughput (HT) System and associated Multi-chip Liver-48 plate.
Presentation
A primary jejunum and primary hepatocyte multi-organ MPS: a promising tool for more predictive studies of human drug ADME and oral bioavailability
ADME studies are a key part of drug discovery, as the evaluation of pharmacological properties determines the efficacy and safety of a given compound. Efforts to improve the in vitro to in vivo translation of drug efficacy and safety data has led to the emergence of more complex microphysiological systems (MPS) that consist of multiple organs that are fluidically linked.
Here, we introduce a multi-organ (Gut/Liver) MPS to profile human oral bioavailability in vitro, that links the intestine and liver using the PhysioMimix® cell culture system, with both cell types being of primary human origin. Liver and intestinal cell lines have absent or low levels of metabolic enzyme expression, and thus fail to predict first pass human metabolism. For the intestinal barrier, crypt epithelium stem/progenitor cells were isolated from the jejunum and expanded on a biomimetic scaffold (RepliGut®). Upon differentiation, the cell layer forms a polarized barrier with a continuous layer of mucus. For the liver, primary human hepatocytes (PHH) are seeded on a 3D collagen-coated scaffold and form microtissues.
We developed a chemically defined media that supports hepatic metabolic functionality and intestinal barrier integrity in the Gut/Liver MPS. We established a validation criteria whereby liver and intestinal cells are first validated separately, then as a functional, fluidically coupled co-culture system. The two independently validated cell types then underwent QC testing in co-culture with the specific context of use in ADME studies using the test compound 7-hydroxycoumarin. The model’s predictive potential for drug ADME and oral bioavailability studies was demonstrated with multiple known compounds.
Here, we present an in vitro human Gut/Liver model that enables intestinal absorption and hepatic clearance to be studied within a system that more precisely recapitulates the human process – versus traditional approaches operating in isolation. We demonstrate maintenance of cell functionality in co-culture and show its predictive potential for drug ADME and bioavailability studies.
Date: Tuesday 3 September
Time: 09:30 – 09:50 (approximately)
Presenter: Dr. Yassen Abbas
Meet the CN Bio Team at DMDG!
Yassen
Dr. Yassen Abbas is a Lead Scientist at CN Bio. He completed an MEng in chemical engineering at The University of Edinburgh and joined the European Space Agency as a graduate engineer. He later received a PhD from the University of Cambridge and completed a postdoc fellowship, also at Cambridge on the development of a tissue engineered model of the human endometrium. He has experience with real-time sensor technology, organoids and development of in vitro tissue models using human primary cells. Dr Abbas has published five peer-reviewed scientific articles, four as first author.
Adrian
A seasoned business developer with extensive commercial experience in the life science sector, Adrian Rea joined CN Bio as the European Director of Sales in June 2022. He brings valuable experience in the 3D cell culture market from his most recent role at InSphero, where he was responsible for developing business opportunities in European and Asian markets. He was previously Sales Director at Enzo Life Sciences, where he managed the restructuring of the global distributor sales channels and expanding the European sales operations. Adrian graduated from the University of Glasgow and received his PhD in pharmacology from Glasgow Caledonian University.