Stem and progenitor cells for liver regenerative medicine

Orthotopic liver transplantation is the gold standard treatment for end stage liver disease or inborn errors of liver metabolism. However organ shortage, severity of the surgical procedure and risks related to graft loss have stimulated the exploration of less invasive strategies. Liver cell transplantation has demonstrated short to medium-term efficacy in correcting inborn errors of metabolism and could offer a valuable bridging treatment for patients with acute liver failure awaiting liver transplant. However, hepatocyte transplantation in the clinic has shown important limitations including transient effect of donor cells, low proportion of engraftment and repopulation, poor resistance of hepatocytes to cryopreservation procedures and also shortage of procurement. Thus while hepatocyte transplantation remains a promising alternative to liver transplantation, replacement of hepatocytes by proliferating stem cells seems likely to circumvent many of the aforementioned obstacles. Building on the demonstration that various stem and progenitor cells can differentiate in vitro and in vivo into hepatocyte-like cells, these cells are now being investigated as an alternative to hepatocytes in liver regenerative medicine. In this study, we concentrate on cells sourced from human adult tissues only as the use of embryonic or fetal material still faces major ethical, safety and/or feasibility concerns. We summarize here the major progresses that have been achieved as regards the isolation and characterization of potential stem and progenitor cell candidates for liver cell therapies both from intra-and extra-hepatic sources. We also discuss animal transplantation data as well as considerations about the carcinogenic risk of such cell therapies. © 2012 The authors and IOS Press. All rights reserve