Liver regeneration after partial hepatectomy

肝脏再生背后的相互作用网络是强大和精确的，肝脏切除导致受控的增殖(细胞增殖)，当肝脏恢复失去的质量时，这种增殖终止。细胞因子和生长因子的相互作用导致这种增生的开始和终止还不是很清楚。我们根据肝脏切除的已知数据，为这种相互作用的网络开发了一个模型。该模型再现了已发表的有关肝再生的数据，并为实验观察提供了几何洞察力。 我们正在与托马斯·杰斐逊大学(Thomas Jefferson University)的移植外科医生多利亚博士合作，看看我们的大鼠肝脏再生模型需要做出哪些改变，才能预测人类的这一过程。目的是确定我们的大鼠肝脏模型中许多参数中的哪些需要改变，以解释人类的过程，这似乎需要大约20倍于大鼠的时间。我们发现，所有大鼠肝再生的生物化学都可以在人类肝再生中被视为不变的。然而，我们发现，模型中描述细胞周期的现象学部分需要结构上的改变，因为不可能使用参数改变的大鼠模型来描述我们从合作者Doria博士那里获得的五个活体供体体积数据。 结果表明，人肝细胞的增殖可能依赖于对肝细胞的代谢应激。因此，大范围切除会导致细胞周期恢复较慢的速度，随着肝质量的恢复和每肝细胞代谢应激的减少而增加。有了这一结构变化，我们能够适应现有的人类数据，我们希望能够访问更大的人类数据数据库，以便更深入地了解这些结构变化。

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 is 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.