Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 31, 2020; 10(3): 64-78
Published online Mar 31, 2020. doi: 10.5500/wjt.v10.i3.64
Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure: A systematic review
Tomoaki Furuta, Kinji Furuya, Yun-Wen Zheng, Tatsuya Oda
Tomoaki Furuta, Kinji Furuya, Yun-Wen Zheng, Tatsuya Oda, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba-shi 305-8575, Ibaraki, Japan
Yun-Wen Zheng, Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Yun-Wen Zheng, Department of Regenerative Medicine, School of Medicine, Yokohama City University, Yokohama 236-0004, Japan
Yun-Wen Zheng, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Author contributions: Furuta T conceptualized and designed the review together with Furuya K and Zheng YW; Furuta T and Furuya K carried out the analysis; Furuta T drafted the initial manuscript; all authors reviewed and approved the final manuscript as submitted; Furuta T and Furuya K contributed equally to the work; Zheng YW and Oda T are senior authors.
Supported by National Natural Science Foundation of China, No. 81770621; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 18H02866; and Japan Science and Technology Agency-Japan International Cooperation Agency's (JST-JICA) Science and Technology Research Partnership for Sustainable Development (SATREPS) Project, No. JPMJSA1506.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Yun-Wen Zheng, PhD, Associate Professor, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba-shi 305-8575, Ibaraki, Japan.
Received: December 4, 2019
Peer-review started: December 4, 2019
First decision: December 12, 2019
Revised: February 10, 2020
Accepted: March 23, 2020
Article in press: March 23, 2020
Published online: March 31, 2020

Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies investigating alternative therapies are plenty. Nevertheless, no study has comprehensively analyzed these therapies from different perspectives.


To summarize the current status of alternative transplantation therapies for OLT and to support future research.


A systematic literature search was performed using PubMed, Cochrane Library and EMBASE for articles published between January 2010 and 2018, using the following MeSH terms: [(liver transplantation) AND cell] OR [(liver transplantation) AND differentiation] OR [(liver transplantation) AND organoid] OR [(liver transplantation) AND xenotransplantation]. Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation. Among them, we selected articles including in vivo transplantation.


A total of 89 studies were selected. There are three principle forms of treatment for liver failure: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Xeno-organ transplantation was covered in 14 articles, scaffold-based transplantation was discussed in 22 articles, and cell transplantation was discussed in 53 articles. Various types of alternative therapies were discussed: Organ liver, 25 articles; adult hepatocytes, 31 articles; fetal hepatocytes, three articles; mesenchymal stem cells (MSCs), 25 articles; embryonic stem cells, one article; and induced pluripotent stem cells, three articles and other sources. Clinical applications were discussed in 12 studies: Cell transplantation using hepatocytes in four studies, five studies using umbilical cord-derived MSCs, three studies using bone marrow-derived MSCs, and two studies using hematopoietic stem cells.


The clinical applications are present only for cell transplantation. Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations, which warrants future research to find relevant clinical applications.

Keywords: Cell transplantation, Liver transplantation, Organ transplantation, Xenotransplantation, Tissue engineering, Scaffold

Core tip: This systematic review analyzes the current status of transplantation treatments in place of liver organ transplantation from multiple viewpoints. We classified reports into three types: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Clinical application occurred for cell transplantation with hepatocytes and mesenchymal stem cells; however, the effect was limited. On the other hand, scaffold-based transplantation is a comprehensive treatment that combines organ transplantation and cell transplantation. Future research for clinical application is expected. The present article provides researchers with a summary and updated information on recent trends in alternatives to liver transplantation and support for future research.