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World J Gastroenterol. Mar 21, 2017; 23(11): 1974-1979
Published online Mar 21, 2017. doi: 10.3748/wjg.v23.i11.1974
Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells
Ryoichi Sakiyama, Brandon J Blau, Toshio Miki
Ryoichi Sakiyama, Brandon J Blau, Toshio Miki, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States
Author contributions: Sakiyama R, Blau BJ and Miki T contributed equally to this work; Sakiyama R, Blau BJ and Miki T performed the majority of the writing; Sakiyama R and Miki T performed data acquisition, analysis; Miki T performed the design, modification and verification.
Supported by the Baxter International Foundation/Keck Summer Research Fellowship Award (to Blau BJ); and the California Institute for Regenerative Medicine, No. RT3-07670 (to Miki T).
Conflict-of-interest statement: The authors state no financial and non-financial 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: Toshio Miki, MD, PhD, Assistant Professor of Research, Department of Surgery, Keck School of Medicine, University of Southern California 2011 Zonal Avenue, HMR 509A, Los Angeles, CA 90033, United States. toshiomi@usc.edu
Telephone: +1-323-4427703 Fax: +1-323-4424040
Received: August 4, 2016
Peer-review started: August 5, 2016
First decision: November 21, 2016
Revised: December 2, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: March 21, 2017
Processing time: 227 Days and 7.6 Hours
Abstract

There is currently a pressing need for alternative therapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver (BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells (hPSCs). In this mini-review, we summarize previous clinical trials with different BAL systems, and discuss advantages of and potential obstacles to utilizing hPSC-derived hepatic cells in clinical-scale BAL systems.

Keywords: Artificial liver; Clinical trial; Hepatocytes; Pluripotent stem cells; Bioreactors

Core tip: The current lack of transplantable donor livers in the world has led to the development of extracorporeal liver support systems as one possible approach to overcome this problem. Bioartificial liver (BAL) support systems require a cell source to replicate human liver function, yet the ideal cell source for this purpose has yet to be determined. Highly-functional hepatocyte-like cells have recently been generated from human pluripotent stem cells, which show promise as a potential cell source in BAL support systems for the treatment of liver failure in the future.