Computational Modeling as an Approach to Study the Cellular and Molecular Regulatory Networks Driving Liver Regeneration

Liver regeneration is a complex process for which the underlying mechanisms are yet to be fully understood. We summarize the recently emerging literature on the application of computational modeling methods to study the mechanisms of liver regeneration. We extended a previously published coarse-grain model of liver regeneration and simulated a wide range of scenarios. We categorized the dynamic tissue mass recovery profiles as corresponding to delayed, enhanced, delayed and enhanced, or suppressed regeneration modes, consistent with multiple disease phenotypes. Sensitivity analysis of the model revealed that the regeneration phenotype is most impacted by the physiological parameters and the kinetics of nonparenchymal cells. We discuss the limitations of the present model and propose future directions, particularly by exploiting the data yielded by emerging approaches to study single-cell scale regulatory networks.