PhD defence E. Gore

Integrating an ex vivo model into fibrosis research

Fibrosis, the tissue response to continuous injury and improper wound healing leading to excessive extracellular matrix deposition, is a progressive condition that can affect many organs and leads to high morbidity and mortality. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Emilia Gore conducted her research on a model that could accelerate the development of an antifibrotic drug. The model is precision-cut tissue slices (PCTS), which preserves the cellular and architectural structure of an organ. The culture of PCTS induces a fibrogenic response, allowing the investigation of fibrosis initiation (culturing healthy tissue slices) and progression (culturing diseased tissue slices), together with fibrosis reversal (testing antifibrotic compounds).In this thesis, Gore advanced the understanding of mouse and human PCTS by exploring the biological changes during culture with an extensive transcriptional analysis. Additionally, she developed a model of non-alcoholic steatohepatitis (NASH) – fatty liver – by using PCTS from mouse models of this condition. PCTS replicated central features of NASH and the model proved suitable to evaluate possible treatments. She also explored the possibility of fibrosis treatment through the inhibition of a central fibrosis pathway, and described in her thesis a potential preclinical marker for advanced liver fibrosis. The studies presented in this thesis reinforce the use of PCTS for fibrosis research.

Promotores: Prof.dr. P. Olinga