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
Research background

Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, the shortage of donor organs limits its application. To overcome this problem, many researchers have attempted to develop alternatives to OLT.

Research motivation

There are several reports of alternative therapies. Nevertheless, no study has comprehensively analyzed these therapies from varying perspectives.

Research objectives

This systematic review aims to summarize the current status of alternative transplantation therapies for OLT and to support future research.

Research methods

A systematic review was performed by searching the PubMed, Cochrane Library and EMBASE databases for studies concerning alternative transplantation therapy for OLT. We used the following MeSH terms: “liver transplantation”, “cell”, “differentiation”, “organoid”, and “xenotransplantation”. Various types of studies were retrieved for full-text evaluation. Of these, we selected articles involving in vivo transplantation.

Research results

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

Research conclusions

This systematic review summarized alternative therapies for OLT from varying perspectives. Alternative therapies have been deeply researched, particularly xeno-organ, scaffold-based, and cell transplantation. Clinically, only cell transplantation with hepatocytes and MSCs have been applied. Scaffold-based transplantation is a comprehensive treatment that combines xeno-organ and cell transplantations. Future research on the clinical application of scaffold-based transplantation is expected.

Research perspectives

This systematic review describes the current status of alternative therapy for OLT in end-stage liver failure. Further studies are needed for clinical applications in the future.