Sinusoidal cell communication in liver fibrosis

Liver fibrosis is a consequence of chronic liver disease characterized by large amounts of scar being produced. On a long term this scar tissue will replace functional liver cells and leads to organ failure.
The only treatment for end-stage liver disease is a liver transplantation. While in current clinical
trials, there are some promising drugs in the pipe-line a complete resolution of liver fibrosis is not observed. A better understanding of the fibrosis process is therefore needed. From mouse studies it is known that hepatic stellate cells are the main producers of the fibrotic scar tissue, which makes these cells interesting targets for anti-fibrotic drug-development. Current knowledge about these cells, is mostly obtained from mouse studies, in whole animals or in laboratory dish (in vitro) models. In mice it is already shown that stellate cell activation; the process leading to scar deposition; is different in whole organisms compared to in vitro models. The aim of our current
proposal is to develop an innovative model to study stellate cells in a complex environment with other liver cell types and to address the role of cell-cell communication during liver fibrosis. It will lead to multiple outcomes: a better in vitro model to study mechanisms of stellate cell activation
and to evaluate which drugs can counter the activation process and thus chronic liver disease progress.