Join us at SOT 2022
We are delighted to be attending SOT’s 61st Annual Meeting and ToxExpo.
The Society of Toxicology (SOT) are dedicated to creating a safer and healthier world by advancing the science and increasing the impact of toxicology.
Head to our exhibition booth – #1727
We look forward to meeting you to discuss how to improve the predictability of human toxicity using organ-on a chip. Reveal the mechanisms of drug-induced liver injury (DILI) with PhysioMimix™ OOC single-and multi organ microphysiological systems.
You can also catch us at two events
Exhibitor hosted session
Liver Microphysiological Systems to Assess Efficacy and Toxicity – Building Robust and Reliable Models for Translational Preclinical Research. Dr. Tomasz Kostrzewski, VP Science & Technology CN Bio & Maureen Bunger, Senior Product Manager Lonza Cell & Gene.
Assessing Drug-Induced Liver Injury Using a Sensitive and Selective Human Liver Microphysiological System and Clinical Biomarkers. Abstract Number/Poster Board number: 4444/P444
Exhibitor hosted session with Lonza
Liver Microphysiological Systems to Assess Efficacy and Toxicity – Building Robust and Reliable Models for Translational Preclinical Research
Microphysiological systems (MPS) are cutting-edge cell culture technologies that emulate the physiological microenvironment and functionality of human organs. Here we discuss how to rapidly and reliably integrate liver MPS into drug discovery and development workflows to gain translational pre-clinical data.
Date: March 28, 2022
Time: 03:00 PM-04:00 PM
Hosted by: Lonza and CN Bio
Presentation from: Dr. Tomasz Kostrzewski, CN Bio & Maureen Bunger, Senior Product Manager Lonza Cell & Gene.
Our poster presentation
Assessing Drug-Induced Liver Injury Using a Sensitive and Selective Human Liver Microphysiological System and Clinical Biomarkers
Drug-induced liver injury (DILI) remains the most common cause for acute liver failure in the USA and Europe and is a leading cause of attrition of compounds in drug development. As an alternative to classical 2D cell cultures, which have significant limitations in assessing DILI, we have developed a human liver microphysiological system (MPS) comprised of human primary liver hepatocyte parenchymal and non-parenchymal cells (NPCs), cultured in 3D microtissues on an engineered scaffold under perfusion up to two weeks. The methodology has been validated with a broad set of twelve severely and mildly hepatotoxic test articles with a variety of chemical composition. Liver function following drug exposure was assessed by a broad spectrum of functional liver-specific endpoints on the cellular structures and culture medium, including clinical biomarkers – alanine aminotransferase (ALT), to create a distinct mechanistic “signature of hepatotoxicity.” The MPS in vitro model showed superior sensitivity and specificity over classic 2D primary hepatocytes (PHHs) cultures and even some standard non-MPS 3D models in detecting DILI (sensitivity 70%, specificity 100%), and identified compounds of high clinical DILI concern that were not detected by some 2D PHHs cultures (levofloxacin) and detected mild toxicity in compounds of low-DILI concern (pioglitazone). By using a wide range of biomarkers, the liver model can detect toxicities in compounds that otherwise might be missed when using only basic cell viability endpoints. The liver MPS enables the analysis of clinical biomarkers, such as ALT, which are notoriously difficult to detect in vitro allowing improved translation to clinical data. Overall, we demonstrate that the liver MPS model is well suited to exploring the molecular mechanisms that underlie DILI and its association with hepatic toxicity. The model can additionally be used to assess how novel compounds behave in distinct patient subsets and how toxicity profiles may be affected by liver disease state (e.g., viral hepatitis, fatty liver disease).
Location: CC Exhibit Hall (Hall B)
Date: Wed, Mar 30
Time: 10:45am – 12:30pm (Pacific)
Authors: O. Novac, R. Silva, L. Young, K. Lachani, D. Hughes, and T. Kostrzewski. CN Bio Innovations, Cambridge, United Kingdom. Sponsor: R. Cardoso