Keeping it Real: Why P450 Assays are Required to Predict Human Drug Responses Using Liver-on-a-Chip
This webinar is part of the 3D Cell Biology Webinar Series.
In this webinar, you will learn:
- Why there’s a pressing need for preclinical assays that predict human responses to drugs
- How organ on a chip addresses traditional in vitro and animal model limitations to provide a solution
- The importance of quality controls during development of complex 3D models
- How Promega’s luminescent P450-Glo™ CYP450 activity assays work and how they can be applied to 3D models
Summary
Despite billions in annual investment, most drugs never reach the market because preclinical experiments fail to predict human effects. Unfortunately, standard in vitro assays need physiological relevance, whilst animal models lack human relevance. By better replicating human organs and tissues in the laboratory, Organ-on-a-chip (OOC) technologies offer the potential to address these limitations. Over the last few years, an impressive effort towards recreating in vitro human organ physiology and function has been made. By coculturing primary human cells in a 3D environment, in the presence of microfluidics to mimic blood flow, it is possible to form lab-grown tissue mimics. Such an achievement requires investigational knowledge about the tissue’s health and functionality using sensitive assays with broad dynamic ranges. Hence, validation and monitoring of the cell health and functionality throughout the experiment becomes a critical step in the development of adoptable and cost-effective tissue model in OOC platforms.
In this webinar, Dr Atefeh Mobasseri, Field Application Scientist at CN Bio, will discuss the use of Promega P450-Glo™ Assay kit as a critical step in cell quality control to assess the metabolic activity of a liver-on-a-chip model, developed by CN Bio, using their bespoke PhysioMimix™ Organ-on-a-chip technology. This liver model has been shown to be highly reliable to assess drugs for safety and efficacy but also to develop liver disease models, to name a few. The key points for successful outcomes are firstly qualifying cells to be able to form a highly functional 3D micro tissue and secondly monitoring metabolic activity of micro tissue throughout the long term experiments. Here, we will show how monitoring CYP450 activity, such as CYP3A4 and CYP1A2, routinely can give a realistic overview of a liver culture’s health and ensure proper assessment of a drug metabolism as well as any potential metabolite-driven toxicity. Dr. Darren Heywood from Promega will introduce cell-based assays optimized for 3D cell culture, including a suite of P450-Glo™ Assays.
Other webinars in this series:
Setting Up Easy-to-Analyze Physiologically Relevant 3D Cultures for in vitro Studies
Ask the Experts: 3D Cell Culture and Assays
Development of 3D Liver Spheroid Cultures and Tools for 3D Culture Metabolic Studies
Using Transcriptomics to Study Drug-Induced Liver Injury in 3D Cellular Models
Speakers
Darren Heywood, PhD
Product Manager, Cell Health
Promega UK
Darren received his PhD in Neurobiology from the University of Bristol in 2003. His research was focused on investigating the involvement of signaling pathways involved in mediating neuronal cell death. Currently, as a Product Manager at Promega UK, Darren manages the cell health portfolio and has a particular interest in tools to monitor 3D cell health. With the demand for more physiologically relevant models comes a need for more accurate and sensitive cell-based assays that can deliver reliable results in more complex 3D microtissues. Darren works to support customers who wish investigate cell health in both 2D and 3D cultures.
Atefeh Mobasseri, PhD
Field Application Scientist
CN-Bio
Atefeh, Field Application Scientist at CN Bio, has an extensive background in tissue engineering and regenerative medicine. Before joining CN Bio, she gained a PhD in Biomedical materials from the University of Manchester and carried out postdoctoral roles at the University of Manchester and Kings College London investigating the interaction, and effect, of 3D scaffolds on cellular behaviour. Since joining CN Bio, she has been supporting their European customers in using CN Bio’s range of PhysioMimix™ systems to generate high content, human-relevant, data.