A predictive computational model shows that biomechanical cell cycle progression control can explain liver regeneration after partial hepatectomy
Résumé
Partial hepatectomy (PHx) is a surgical intervention where a part of liver is removed. Due to its extraordinary capacity to regenerate, the organ is able to regenerate about two-thirds of its mass within a few weeks. Nevertheless, in some patients, regeneration fails. Understanding the principles and limitations underlying regeneration may permit to control this process. We established a computational model to mimic and prospectively improve regeneration of the liver lobe of mice. This model represents each hepatocyte individually and builds upon a previous computational model of regeneration of drug (CCl4)-induced damage in a single liver lobule, a small subunit of a lobe. The present study simulates entire liver lobes that can consist of hundreds to thousands of lobules. Different from that previous model it accounts for biomechanical control of cell cycle progression (Biomechanical Growth Control). The model reproduced the available experimental observations only if BGC was taken into account. Interestingly, the model predicted that BGC minimizes the number of proliferating neighbor cells of a proliferating cell resulting in a checkerboard-like proliferation pattern. Moreover, the model predicted different cell proliferation patterns in pigs and mice that corresponded to data obtained from regenerating tissue of the two species. In conclusion, the here established model suggests that biomechanical control mechanisms may play a significant role in liver regeneration after PHx.
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