The pros and cons of 3D in vitro culture models of liver fibrosis
November 4, 2019
10:00 AM - 11:00 AM US EST
Presenter: Prof. Leo A. van Grunsven, Vrije Universiteit Brussel
Chronic liver disease is the major cause of progressive liver fibrosis which, in turn, leads to cirrhosis of the liver. One major obstacle in the development of efficient therapies is the lack of robust and representative in vitro models of human liver fibrosis to aid in understanding the basic mechanisms of the disease and in the development phase of pharmaceuticals.
The aim of this presentation is to give some background on the mechanisms involved in liver fibrosis development and why our work is based on the central hypothesis that liver fibrosis in vitro cannot be studied using only hepatic stellate cells (HSCs)–the main producer of scar tissue during fibrosis. I will present and discuss some results and problems we faced while developing an in vitro liver fibrosis model. We established a model in which HepaRG cells (Biopredic) were co-cultured with either in-house isolated HSCs or in-house differentiated induced pluripotent stem cell derived HSCs. In both cases, exposure to hepatotoxins resulted in hepatocytic damage and consequent HSC activation. We now work on a model using only primary mouse HSCs and hepatocytes. I will also discuss some of our work aiming at developing more complex primary mouse co-cultures for liver disease modeling and briefly address the work of other groups that reported on such complex in vitro culture systems.