Towards improved hepatocyte cultures: Progress and limitations

Food Chem Toxicol. 2020 Apr:138:111188. doi: 10.1016/j.fct.2020.111188. Epub 2020 Feb 8.

Abstract

Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market. Therefore, there is an urgent need for reliable predictive in vitro tests, which unfailingly identify hepatotoxic drug candidates, reduce drug development time, expenses and the number of test animals. Currently, human hepatocytes represent the gold standard. However, the use of hepatocytes is challenging since the cells are not constantly available and lose their metabolic activity in culture. To solve these problems many different approaches have been developed in the past decades. The aim of this review is to present these approaches and to discuss the possibilities and limitations as well as future opportunities and directions.

Keywords: 3D culture; 3D micro-tissues; Co-culture; In vitro toxicity testing; Organ-on-a-chip; Primary human hepatocytes.

Publication types

  • Review

MeSH terms

  • Activation, Metabolic
  • Cell Culture Techniques*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / therapy*
  • Coculture Techniques
  • Culture Media / chemistry
  • Drug Development
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Liver Failure, Acute / complications
  • Liver Failure, Acute / diagnosis
  • Models, Animal
  • Spheroids, Cellular
  • Tissue Scaffolds

Substances

  • Culture Media