MRC Centre for Regenerative Medicine, 5 Little France Drive, University of Edinburgh, Edinburgh EH16 4UU, UK.
Birmingham National Institute for Health Research (NIHR) Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Vincent Drive Birmingham, B15 2TT, UK.
Nat Rev Gastroenterol Hepatol. 2016 Aug;13(8):473-85. doi: 10.1038/nrgastro.2016.97. Epub 2016 Jun 29.
Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsic to the liver interact to initiate and regulate liver regeneration. Less well understood, and more clinically relevant, are the factors at play when the abnormal liver is required to regenerate. Fatty liver disease, chronic scarring, prior chemotherapy and massive liver injury can all inhibit the normal programme of regeneration and can lead to liver failure. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or directly stimulate liver regeneration. Although animal models of liver regeneration have been highly instructive, the clinical relevance of some models could be improved to bridge the gap between our in vivo model systems and the clinical situation. Likewise, modern imaging techniques such as spectroscopy will probably improve our understanding of whole-organ metabolism and how this predicts the liver's regenerative capacity. This Review describes briefly the mechanisms underpinning liver regeneration, the models used to study this process, and discusses areas in which failed or compromised liver regeneration is clinically relevant.
肝脏再生已经研究了几十年，肝脏在切除或中度损伤后正常再生的机制已得到很好的描述。大量的外在因素（如胆汁酸和循环生长因子）和内在因素相互作用，启动并调节肝脏再生。了解较少但更具临床相关性的是异常肝脏需要再生时起作用的因素。脂肪肝疾病、慢性瘢痕、先前的化疗和大量肝损伤都可能抑制正常的再生程序，并导致肝功能衰竭。了解这些机制可以使我们能够合理地针对特定的治疗方法，要么减少抑制再生的因素，要么直接刺激肝脏再生。尽管肝脏再生的动物模型具有高度的启发性，但某些模型的临床相关性可以通过缩小我们的体内模型系统与临床情况之间的差距来提高。同样，现代成像技术（如光谱）可能会提高我们对整个器官代谢的理解，以及这如何预测肝脏的再生能力。这篇综述简要描述了肝脏再生的机制、用于研究这一过程的模型，并讨论了在临床相关的失败或受损的肝脏再生的领域。
