Three-dimensional culture of hepatocytes for prediction of drug-induced hepatotoxicity

Importance of the field: Hepatotoxicity is the most frequent reason for the withdrawal of an approved drug from the market. Monolayer culture of hepatocyte in two-dimension, which is relatively inexpensive, convenient and easy to use, serves a traditional hepatocyte-based high-content screening for identifying hepatotoxic side effects of tested drugs. However, two-dimensional methods have their limitations in lack of insensitivity on reflection of drug hepatotoxicity. Three-dimensional (3D) cultures of hepatocytes in sandwich, spheroid and gel entrapment provide a microenvironment for high expression of liver-specific functions and are being proposed for prediction of drug hepatotoxicity. Areas covered in this review: This review addressed the reliability of 3D culture models on screening hepatotoxic drugs with particular emphasis on gel entrapment culture model due to its more systematic data on drug testing. What the reader will gain: The reader will gain a comprehensive understanding of the improved prediction efficacy of 3D culture models. Take home message: Hepatocytes in 3D cultures, although in need of further standardization required by the throughput operation, show great potential in attempts to ensure the efficacy on prediction of drug hepatotoxicity.