The network of interactions underlying liver regeneration is robust and precise with liver resections resulting in controlled hyperplasia (cell proliferation) that terminates when the liver regains its lost mass. The interplay of cytokines and growth factors responsible for the inception and termination of this hyperplasia is not well understood. We developed a model for this network of interactions based on the known data of liver resections. This model reproduces the relevant published data on liver regeneration and provides geometric insights into the experimental observations. We are collaborating with Dr. Doria, a transplant surgeon at Thomas Jefferson University, to see what changes are required in our model of rat liver regeneration to be able to predict the process in human.
The aim i s to ascertain which of the numerous parameters in our rat liver model needs to be changed to account for the human process, which appears to take roughly 20 times as long as that in rat. We have found that all the biochemistry of rat liver regeneration can be treated as unchanged in human liver regeneration. We have found, however, that the phenomenological part of the model that describes the cell cycle needs a structural change, as it is not possible to use the rat model with changed parameters to describe the five human live donor volume data we have obtained from our collaborator, Dr. Doria. It turns out that human hepatocyte proliferation may be dependent on the metabolic stress on the hepatocytes. Thus, a large resection leads to a slower rate of cell cycle progress in recovery, which increases as liver mass is recovered and the metabolic stress per hepatocyte decreases. With this structural change, we have been able to fit the available human data and we are hoping to obtain access to larger databases of human data in order to obtain more insight into these structural changes.
|Periwal, V; Gaillard, J R; Needleman, L et al. (2014) Mathematical model of liver regeneration in human live donors. J Cell Physiol 229:599-606|