Hepatology Research 36 (2006) 237–247 Review Hepatocyte transplantation: State of the art Fl´ avio Henrique Ferreira Galv˜ ao a,∗ , Dahir Ramos de Andrade J ´ unior b , Dahir Ramos de Andrade b , Bruno Costa Martins c , Allan Garms Marson c , Christiano Vinicius Bernard c , Sˆ ania Alves dos Santos b , Telesforo Bacchella a , Marcel Cerqueira C´ esar Machado a a Laborat´ orio de Transplante Experimental da Disciplina de Transplante e Cirurgia do F´ ıgado (LIM 37), Faculdade de Medicina da Universidade de S˜ ao Paulo, S˜ ao Paulo, Brazil b Laborat´ orio de Bacteriologia e Microbiologia Celular (LIM-54), Faculdade de Medicina, Universidade de S˜ ao Paulo, S˜ ao Paulo, Brazil c Residente de Cirurgia da Faculdade de Medicina da Universidade de S˜ ao Paulo, S˜ ao Paulo, Brazil Received 21 October 2005; received in revised form 29 June 2006; accepted 17 August 2006 Available online 2 October 2006 Abstract Advances in biotechnology have allowed hepatocyte transplantation as a relevant proposition to treat liver disease. This procedure may change the crescent mortality in liver transplantation waiting lists due global organ shortage. Recent clinical trials have described promising results of hepatocyte transplantation for acute, acute-on-chronic and metabolic liver disease. In this report, we discuss progresses regarding hepatocyte culture, cryopreservation systems, hepatocyte immortalization, suitable recipient site for hepatocyte engraftment, cell differentiation and fusion into hepatocytes, current clinical trials, and summarize the bioartificial liver systems. These progressions motivate expectation concerning hepatocyte transplantation as a consistent therapy for liver disease. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Hepatocyte transplantation; Liver transplantation; Xenotransplantation; Cell culture; Liver failure Contents 1. Introduction ........................................................................................................ 238 2. Methods ........................................................................................................... 238 3. Hepatocyte isolation and culture ..................................................................................... 238 4. Cryopreservation ................................................................................................... 239 5. Hepatocyte immortalization .......................................................................................... 239 5.1. Permanent telomeric replication by telomere/telomerase mechanism ............................................... 239 5.2. Gene therapy ................................................................................................. 239 5.3. Replicative senescence ........................................................................................ 240 5.4. Reversible immortalization .................................................................................... 240 6. Hematopoietic stem cells and peripheral blood monocytes differentiation and fusion into hepatocytes ....................... 240 7. Suitable recipient site for hepatocyte implantation and engraftment ...................................................... 241 7.1. Intraportal and intrasplenic infusion ............................................................................ 241 7.2. Ectopic sites for hepatocyte transplantation ..................................................................... 242 ∗ Corresponding author at: Rua Dona Antonia de Queiroz 551, Apt 31, Higienopolis, S˜ ao Paulo 01307-010, SP, Brazil. Tel.: +55 11 98666680/32576478; fax: +55 11 30667000. E-mail address: fgalvao@usp.br (F.H.F. Galv˜ ao). 1386-6346/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.hepres.2006.08.008