Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments

Abstract

Drug failure due to toxicity indicators remains among the primary reasons for staggering drug attrition rates during clinical studies and post-marketing surveillance. Broader validation and use of next-generation 3-D improved cell culture models are expected to improve predictive power and effectiveness of drug toxicological predictions. However, after decades of promising research significant gaps remain in our collective ability to extract quality human toxicity information from in vitro data using 3-D cell and tissue models. Issues, challenges and future directions for the field to improve drug assay predictive power and reliability of 3-D models are reviewed.

Keywords: 3-D organoid culture; Cell culture models; Cellular microenvironment; Drug development; HTS screens; Nanotoxicity; Reasons for failure; Toxicity.