Development of a differentiated hepatic in vitro system for long-term pharmaco-toxicological studies based on (epi)genetic modification of primary hepatocytes

  • Eva Ramboer ((PhD) Student)

Student thesis: Doctoral Thesis

Abstract

Before any new pharmaceutical can enter the market, its efficacy and safety must be ensured through rigorous testing. Over the years, animal studies have been routinely conducted for this purpose. However, the use of living animals for pharmaco-toxicological research has been highly criticized and seems no longer acceptable.
Increasing attention currently goes to the development and use of appropriate in vitro models, especially liver-based testing platforms. Among all the hepatic in vitro models available today, cultures of primary human hepatocytes still remain the gold standard in vitro tool for pharmaco-toxicological studies. Nevertheless, their use is largely impeded by the occurrence of dedifferentiation and the ubiquitous shortage of primary human hepatocytes for research purposes. The present doctoral thesis project tried to contribute to these two yet unresolved difficulties in the field of liver-based in vitro
modelling. In the first part, the use of epigenetically-stabilized primary hepatocyte cultures for long-term testing purposes was explored, with special focus on hepatic drug transporters. The second part was focused on the development and characterization of a new human hepatic cell line.
Date of Award15 Oct 2015
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorMathieu Vinken (Promotor), Tamara Vanhaecke (Promotor), Vera Rogiers (Promotor), Ilse Smolders (Jury), Leo van Grunsven (Jury), Joeri Aerts (Jury), Roosmarijn Vandenbroucke (Jury) & Pieter Annaert (Jury)

Keywords

  • animal studies
  • pharmaco-toxicological research
  • in vitro
  • human hepatic cell line

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