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Partial hepatectomy (PHx) is a surgical intervention where a part of theliver is removed. Due to its extraordinary capacity to regenerate, the liver isable to regenerate about two-thirds of its mass within a few weeks.Nevertheless, in some patients regeneration fails. Understanding the principlesand limitations underlying regeneration may permit to control this process andprospectively improve the regeneration. Here, we established a simulation modelto mimic the process of regeneration in the liver lobe of a mouse. This modelrepresents each hepatocyte individually and builds upon a previouscomputational model of regeneration of drug induced damage in a single liverlobule. The present study simulates entire liver lobes that consist of hundredsto thousands of lobules. It accounts for biomechanical control of cell cycleprogression (Biomechanical Growth Control), which has not been considered inthat previous work. The model reproduced the available experimentalobservations only if BGC was taken into account. Interestingly, the modelpredicted that BGC minimizes the number of proliferating neighbor cells of aproliferating cell resulting in a checkerboard-like proliferation pattern.Moreover, the model predicted different cell proliferation patterns in pigs andmice that corresponded to data obtained from regenerating tissue of the twospecies. In conclusion, the here established model suggest that biomechanicalcontrol mechanisms may play a significant role in liver regeneration after PHx.

Model predicts fundamental role of biomechanical control of cell cycle progression during liver regeneration after partial hepatectomy