Visikol’s Director of Drug Discovery, Peter Worthington Ph.D.,
to Present at
SELECTBIO’s 3D-Cell Culture, Organoids, and Organs-on-Chips Conference

Balancing Cost, Throughput and In Vivo Relevancy for In Vitro Liver Studies

Wednesday, 15 December 2021 at 14:00

While we can generate ever more complex advanced cell culture models for use in our in vitro programs, not all research questions require this level of complexity. Through this presentation, Dr. Worthington will discuss how to balance cost, throughput and in vivo relevancy in the context of drug induced liver injury (DILI) and modeling liver disease (NASH, NAFLD). The presentation will review the use cases and applications for 2D cell culture models, 3D spheroid models and ex vivo precision cut tissue slice model

Peter Worthington Ph.D., Director of Drug Discovery, Visikol Dr. Worthington is the Director of Drug Discovery at Visikol where he oversees the companies advanced cell culture assays and models. Through his time at Visikol, Dr. Worthington has developed several novel 3D cell culture assays and models which the company now leverages to help its clients accelerate their drug discovery and development programs.

Many drug candidates fail during clinical trials and post-market withdrawal due to hepatoxicity or Drug Induced Liver Injury (DILI). Animal studies have proven insufficient to predict these potential failures and risks. Researchers and toxicologist need a better tool or set of tools to assess the risk of hepatoxicity in pre-clinical trials. Many have turned to cell-based assays to evaluate these potential harmful risks. HUREL, a division of Visikol, has developed a long-enduring primary hepatocyte-based co-culture model to assist in the evaluation of hepatoxicity from potential drug candidates.

There are several hepatocyte-based in vitro models that have been developed for the prediction of DILI. One subset of these models is the 2D cell-based monoculture and co-cultures models. The monocultures use either primary hepatocytes or cell lines such as HepG2 or HepaRG. However, monocultures provide limited insight into hepatoxicity because of metabolic loss, decreased cell viability and de-differentiation which does not allow for large experimental windows. A co-culture model has improved metabolic competency and is better at predicting hepatoxic liabilities.

The model developed by HUREL, a multi-species, hepatic co-culture is comprised of cryopreserved primary hepatocytes from human, dog, rat, or other pre-clinical species, with non-parenchymal stromal cell line. This combination of cells allows for hepatocytes to maintain their viability and general cellular competency for two weeks.

In 2017, HUREL scientists published a study on the validation of their co-culture model, alongside Sanofi Pharmaceuticals and Chrysalis Pharma Partners in the journal Toxicology and Applied Pharmacology, “Long-enduring primary hepatocyte-based co-cultures improve prediction of hepatoxicity”. In this study 19 compounds with known hepatotoxicity were evaluated in parallel with 10 proprietary compounds from Sanofi Pharmaceuticals. HUREL’s co-culture model showed greater sensitivity compared to monocultures in their ability to predict eventual outcomes in pre-clinical or clinical settings. This co-culture model was also able to distinguish between structurally and functionally similar compounds that had different potentially hepatotoxic effects. The main advantage to this model is that the longevity of the co-culture allows for the necessary time to see an accumulative effect on the hepatocytes from compounds. Evaluating time-based toxicity can facilitate earlier decision making based on repeated dosing results. Overall, the ability to obtain this data early on in the drug discovery/developmental pipeline has the ability to avoid late-stage failure of drug candidates that is currently an issue.

Visikol is committed to furthering and achieving our client’s goals in drug discovery. Contact us to work with our expert team of scientist.