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. Live donor liver transplants (LDLT) are increasingly used to treat end-stage liver diseases such as hepatocellular carcinomas, non-alcoholic fatty liver disease, primary sclerosing cholangitis, and others, due to shortages of cadaveric organs. LDLT have the advantage of proactive treatment before the recipients condition deteriorates, but rare complications have occurred in donors. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was undertaken to investigate the risks and benefits to LDLT donors and recipients. A subset of donors in the A2ALL study was recruited for a detailed 6-month study of hepatic function and regeneration known as the DQLFT (Donor Quantitative Liver Function Tests) study (1). Liver volume measurements and blood measurements were taken at 4 time points (0 days, 4 days, 3 months, 6 months post-surgery) from these donors. The DQLFT study was distinct in that it quantified liver regeneration during the initial 2-week period when human livers regenerate most quickly (2-6). This detailed data led us to make improvements in a mathematical model of rat liver regeneration developed by Furchtgott et al. (7) and adapted with limited data for human liver regeneration by Periwal et al. (8) Finally, liver regeneration has been studied in several other mammals besides humans and rats, such as mice, pigs, dogs, and rabbits. In this study, we tested the hypothesis that only varying the metabolic load parameter between species while keeping all other cell cycle and biochemical parameters constant would allow us to predict liver regeneration in five mammalian species: mouse, rat, dog, rabbit and human.
| 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 |
