CRAIG SIMMONS

Three-Dimensional Liver Tissue Models for High-Throughput Screening of the Efficacy and Hepatotoxicity of Drugs

Challenge: Poor efficacy and unpredictable toxic effects are leading causes for the removal of drugs from the market. Many drugs act unpredictably in patients because the preclinical studies fail to accurately model human biology. In particular, the liver requires special attention as it is responsible for metabolizing drugs. Thus, improved liver models could identify and eliminate toxic and ineffective drugs earlier in the drug discovery process.

Solution: To meet this need, the team has developed three-dimensional liver microtissues that demonstrate improved functionality over standard liver models. The team incorporates these microtissues in a microfluidic platform to model arrays of tissue containing blood vessels. This new and improved liver model is unique in its compatibility with standard laboratory equipment and the pharmaceutical industry R&D processes, ensuring ease of implementation with minimal time and effort. The new liver model is optimised to achieve functionality more similar to native human liver tissue than is possible with conventional models. The system was validated to improve liver cell viability and metabolic function compared with conventional models.

Achievements/Impact: At project completion, the team should deliver a new best-in-class model of human liver tissue that better mimics human biology. This platform should decrease drug attrition as well as the time and cost associated with drug development, by identifying toxic drugs prior to initiation of clinical studies.

Principal Investigator:

Craig Simmons
University of Toronto

Co-investigators

Michael Sefton, Denis Grant, M. Dean Chamberlain
University of Toronto

Ongoing Project
$300,000 / 2 years
Supported by CQDM through:
• Pfizer
• Merck
• GSK
• Janssen
• Sanofi
• Boehringer Ingelheim
• Novartis
• BL-NCE
And by co-funding partner:
• OCE