Recent advances in three-dimensional cell culturing to assess liver function and dysfunction: from a drug biotransformation and toxicity perspective

Abstract

The liver is a vital organ fulfilling a central role in over 500 major metabolic functions, including serving as the most essential site for drug biotransformation. Dysfunction of the drug biotransformation processes may result in the exposure of the liver (and other organs) to hepatotoxins, potentially interacting with cellular constituents and causing toxicity and various lesions. Hepatotoxicity can be investigated on a tissue, cellular and molecular level by employing various in vivo and in vitro techniques, including novel three-dimensional (3 D) cell culturing methods. This paper reflects on the liver and its myriad of functions and the influence of drug biotransformation on liver dysfunction. Current in vivo and in vitro models used to study liver function and dysfunction is outlined, emphasizing their advantages and disadvantages. The advantages of novel in vitro 3 D cell culture models are discussed and the possibility of novel models to bridge the gap between in vitro and in vivo models is explained. Progression made in the field of cell culturing methods such as 3 D cell culturing techniques over the last decade promises to reduce the use of in vivo animal models in biotransformation and toxicological studies of the liver.

Keywords:

• 3D models
• drug biotransformation
• drug toxicity
• in vitro models
• liver dysfunction

Acknowledgements

Opinions expressed, and conclusions arrived at, are those of the author and are not necessarily to be attributed to the NRF or the MRC.

Disclosure statement

The authors declare no conflict of interests.

Additional information

Funding

This work was supported by the National Research Foundation (NRF) of South Africa under Grant number [91460]; the South African Medical Research Council (MRC) under Self-Initiated Research grant and DrugMode A/S and MC2 Biotek (Denmark). We would also like to acknowledge the support of the COST actions CM1407 (Challenging organic synthesis inspired by nature - from natural products chemistry to drug discovery) and CA16119 (In vitro 3-D total cell guidance and fitness).