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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 24, 2016; 6(1): 42-53
Published online Mar 24, 2016. doi: 10.5500/wjt.v6.i1.42
Immunological aspects of liver cell transplantation
Felix Oldhafer, Michael Bock, Christine S Falk, Florian W R Vondran
Felix Oldhafer, Florian WR Vondran, Regenerative Medicine and Experimental Surgery (ReMediES), Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany
Michael Bock, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
Michael Bock, Christine S Falk, Florian WR Vondran, German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 30625 Hannover, Germany
Christine S Falk, Institute of Transplant Immunology, Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by Grants of the German Research Foundation (DFG, SFB 738; projects B3, C11) and BMBF 01EO1302.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: PD Dr. Florian WR Vondran, MD, Regenerative Medicine and Experimental Surgery (ReMediES), Department of General, Visceral and Transplant Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. vondran.florian@mh-hannover.de
Telephone: +49-511-5326317 Fax: +49-511-5328326
Received: July 31, 2015
Peer-review started: August 1, 2015
First decision: October 13, 2015
Revised: October 21, 2015
Accepted: December 7, 2015
Article in press: December 8, 2015
Published online: March 24, 2016
Processing time: 230 Days and 22.4 Hours
Abstract

Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells.

Keywords: Liver cell transplantation; Cell-based therapy; Hepatocyte transplantation; Transplant immunology; Regenerative medicine

Core tip: Failure of durable engraftment of transplanted hepatocytes despite application of immunosuppression is mainly attributed to the remaining recipient’s immune responses against these allogenic grafts. Immune responses significantly differ from those observed for transplantation of whole livers and other solid organs. Innate immunity in combination with adaptive immune responses by T- and B-cells have to be taken into account for liver cell transplantation-specific immunosuppressive strategies. Possible clinical solutions to these obstacles will involve new combinations of novel and established immunosuppressive and anti-inflammatory drugs, co-transplantation of other liver cell types or regulatory immune cells. In the future, also (syngenic) liver stem cells will be an option.