In spite of the enormous regenerative capacity of the liver, most dramatically described in the allegory of Prometheus, the effectiveness of cellular treatment for end-stage liver diseases is still limited, with orthotopic liver transplantation being currently the treatment of choice. Nevertheless, long-term success of hepatocyte transplantation for metabolic liver diseases in children has been realised. 1e3 In the light of the severe shortage of available donor organs, the application of hepatocyte transplantation for end-stage liver diseases remains an attractive therapeutic option. However, the underlying molecular and cellular mechanisms preventing the effective use of cellular treatment for end-stage liver diseases need to be better understood in order to improve translation of this technique into clinical use.

The work by Kaldenbach et al4 in the current issue of Gut begins to address these issues by investigating the relevance of hepatocyte growth factor (HGF)/c-Met signalling in vivo for hepatocyte repopulation after transplantation. The authors employed an experimental system that made use of c-Met (loxP/loxP) and hepatocyte-specific conditional c-Met knockout (c-MetÀ/À) mice as donors and/or recipients for hepatocyte transplantation. Two major findings emerged:(1) c-MetÀ/À cells did not repopulate the recipient livers after transplantation indicating that c-Met signalling in donor cells is indispensable for repopulation; and (2) genetic deletion of hepatocyte c-Met in the host recipient liver greatly enhanced the expansion of the wild-type donor hepatocytes (up to 250-fold after 12 weeks). The mechanistic explanations provided included enhanced apoptosis, reduced cellular proliferation, lack of AKT kinase and signal transducer and activator