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Received Nov 4, 2017; Accepted Feb 21, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
The advent of successful liver transplantation, which was initially performed by Starzl et al., shifted the hepatic failure paradigm from an end-stage disease to a treatable condition with meaningful long-term survival, but it also created a new dilemma in that organ supply cannot meet liver transplantation demands [1, 2]. Better organ preservation methods, including the use of HMP, have expanded the donor pool to meet the growing organ demand with the use of marginal grafts.
HMP is an attractive option for avoiding a long warm ischaemia time and minimizing graft metabolic requirements while providing metabolic and oxygenation support. Although broadly implemented in renal transplantation, HMP remains investigational in clinical liver transplantation, with several animal studies showing that liver HMP is safe and, in most cases, superior to simple SCS, but the underlying mechanisms remain speculative [3]. Enhanced hepatocyte proliferation may result in better recovery after cold ischaemic injury and allow partial liver transplantation from donor corpses or living donors [4]. We found better liver graft regeneration with HMP compared with SCS for the first time in our pilot study. Therefore, we sought to determine the underlying mechanisms involved.
HO-1 is a ubiquitously expressed inducible enzyme that degrades haem to carbon monoxide (CO), biliverdin, and Fe2+. It participates in maintaining intracellular homeostasis and plays an important role in protecting cellular organization by reducing oxidative damage, inhibiting cell apoptosis, and attenuating the inflammatory response [5]. Increasing evidence suggests that HO-1 may play a role in protecting against various proliferative disorders, including transplant vascular stenosis, transplant rejection, and ischaemia-reperfusion (IR) injury among many others [6]. Relevant to the studies presented here, inhaled CO at low, nontoxic concentrations has been shown to accelerate liver regeneration in a mouse model of partial hepatectomy [7]. However, no studies have explored the role of HO-1 in recovering liver graft regeneration via HMP, which is the objective of our study.
Among the numerous growth factors with important roles in liver regeneration, HGF is the most notable, which is released from stellate...