title: Liver regeneration - mechanisms and models to clinical application.
abstract: 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.
authors.affiliation: MRC Centre for Regenerative Medicine, 5 Little France Drive, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.affiliation: 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.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Newsome
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D064987:Cell- and Tissue-Based Therapy; D005109:Extracellular Matrix / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging; D008107:Liver Diseases / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D016031:Liver Transplantation / Q000379:methods; D051379:Mice; D023421:Models, Animal; D009929:Organ Size; D051381:Rats; D015027:Zebrafish
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers