Precision-cut liver slices: an ex vivo model for the early onset and end-stage of liver fibrosis

Inge Westra

Research output: ThesisThesis fully internal (DIV)

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Liver fibrosis is a serious complication associated with chronic injury, characterized by excessive deposition of extracellular matrix proteins, and contributes to a further impairment of liver function. Up till now, no antifibrotic drugs are available and therefore patients with end-stage liver fibrosis, cirrhosis, can only be treated with a liver transplantation.
In the research described in this thesis “precision-cut liver slices” were used as ex vivo model in which all cell types of the liver are present. The aim was to investigate liver slices of human and rat livers as model for liver fibrosis and to test antifibrotic drugs.
Successful models were developed for both the early onset and end-stage of liver fibrosis and were applied to study the mechanism of the disease process and to test antifibrotic drugs. It was found that during the early onset of liver fibrosis different mechanisms play a role than during the end-stage of liver fibrosis in these liver slices. Importantly, a clear difference in the mechanism and effect of antifibrotic drugs was found between rat liver slices and human liver slices, which may explain why drugs that appeared effective in animal studies were not successful in the clinic up to now.
The use of this model will lead to a considerable reduction of the use of animal experiments in testing antifibrotic compounds when applied in fibrosis research and drug studies and hopefully to successful antifibrotic drugs and a more reliable prediction of the effects of drugs in humans.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Groothuis, Genoveva, Supervisor
  • Olinga, Peter, Co-supervisor
Award date27-Jun-2014
Place of Publication[S.l.]
Print ISBNs978-90-8891-902-2
Publication statusPublished - 2014

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