The liver has a remarkable capacity to regenerate upon damage or tissue loss. This process is regulated by highly controlled interplay of multiple cytokines and growth factors. One of the key factors promoting hepatocyte proliferation is the hepatocyte growth factor (HGF). In order to study HGF, we constructed a spatio-temporal liver tissue model based on 3D imaging data of liver tissue. The model is able to integrate information on multiple scales, from intracellular events to organ and body level, and thereby can be used to characterize the role of HGF during liver regeneration and specifically how the spatial-temporal proliferation pattern during regeneration is molecularly controlled in time and space. During model simulations of the liver regeneration process, the liver tissue model was constrained by parameters derived at intracellular and cellular level. Interestingly, the model could reproduce the proliferation kinetics observed experimentally. Additionally, the model suggested that a second source of HGF is required to best fit the experimental data.
In sum the integration of experimental data with mathematical modelling applied at a multi-scale level allows to understand the complex regulation of HGF dependent proliferation pattern during liver regeneration.