Section: Application Domains

Liver modelling

Liver is the main detoxifying organ of the human body and can regenerate up to about 70% of its mass. It performs its task by using a complex tissue architecture, with hepatocytes aligning along micro-capillaries and forming a dense network. The incidence rate of liver diseases is steadily increasing, liver cancer ranking 6th among all cancers. About one person in 12, otherwise said 500 million people worldwide, suffer from viral hepatitis. Hepatitis B and C as well as misuse of drugs or alcohol are major causes of liver cancer. Notwithstanding the importance of this public health problem, disease pathogenesis and regeneration in liver are still not well understood.

So far systems biology approaches addressing the tissue scale are rare. Most of those which do so base on compartment models (e.g. (Diaz-Ochoa et. al. Frontiers in Pharmacology, 2013)); only recently are approaches addressing the tissue scale being developed ( [75] , (Ricken, Dahmen, Dirsch, Biomech. Model. Mechanobiol. 2010), (Debbaut et. al., J. Biomech. Eng. 2014), (Siggers, Leungchavphongse, Ho, Repetto, Biomech. Model. Mechanobiol. 2014), (Schwen et. al., PLoS Comput. Biol. 2014)). We are developing a multi-scale model of liver regeneration representing the tissue architecture, the different cell types, the flow systems, hepatocyte metabolism and signal transduction controlling cell cycle entrance in the regeneration processes, taking into account extrahepatic compartments when relevant. Applications are regeneration after drug-induced damage and after partial hepatectomy, drug pharmacodynamics and pharmacokinetics in liver and liver cancer, and model-based prediction of in-vivo drug toxicity from in-vitro measurements (Godoy et al., Arch Toxicol. 2013 Aug;87(8):1315-1530). The research work is performed within the EU project NOTOX, the BMBF project Virtual Liver Network and the ANR project IFLOW.