Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Sep 26, 2015; 5(3): 108-114
Published online Sep 26, 2015. doi: 10.5662/wjm.v5.i3.108
Hepatocyte selection medium eliminating induced pluripotent stem cells among primary human hepatocytes
Minoru Tomizawa, Fuminobu Shinozaki, Yasufumi Motoyoshi, Takao Sugiyama, Shigenori Yamamoto, Naoki Ishige
Minoru Tomizawa, Department of Gastroenterology, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Fuminobu Shinozaki, Department of Radiology, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Yasufumi Motoyoshi, Department of Neurology, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Takao Sugiyama, Department of Rheumatology, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Shigenori Yamamoto, Department of Pediatrics, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Naoki Ishige, Department of Neurosurgery, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, Chiba 284-0003, Japan
Author contributions: Tomizawa M and Shinozaki F wrote this manuscript; Motoyoshi Y, Sugiyama T, and Yamamoto S prepared figures; Ishige N supervised the manuscript.
Conflict-of-interest statement: Nothing to declare.
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: Minoru Tomizawa, MD, PhD, Department of Gastroenterology, National Hospital Organization Shimoshizu Hospital, 934-5 Shikawatashi, Yotsukaido City, Chiba 284-0003, Japan. nihminor-cib@umin.ac.jp
Telephone: +81-43-4222511 Fax: +81-43-4213007
Received: March 10, 2015
Peer-review started: March 18, 2015
First decision: May 13, 2015
Revised: May 22, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: September 26, 2015
Processing time: 190 Days and 0.6 Hours
Abstract

Hepatic insufficiency is a fatal liver disease with a significant decrease in functioning hepatocytes. If hepatocytes could be generated from human induced pluripotent stem (hiPS) cells and transplanted into patients with hepatic insufficiency, the disease may become curable. However, a major limitation to this therapeutic strategy is due to the tumorigenicity of hiPS cells and their ability to form cancer. Current methods for eliminating unwanted hiPS cells use genetic manipulation or reagents that are potentially hazardous for hepatocytes; therefore, revised methods are necessary and anticipated. Glucose and arginine are essential cell culture medium ingredients for the survival of most cells, including hiPS cells. However, hepatocytes can produce its own glucose and arginine through galactokinase and ornithine transcarbamylase, respectively. Therefore, it was hypothesized that unwanted hiPS cells could be eliminated in a medium without glucose and arginine, and supplemented with galactose and ornithine instead. This modified medium has been established as hepatocyte selection medium (HSM). So far, attempts to generate a pure colony of mature hepatocytes from hiPS cells have not been successful. After establishment of co-culture in HSM, primary human hepatocytes survive while hiPS cells die within three days. Our latest results regarding a modification of HSM will be introduced in this manuscript.

Keywords: Ornithine transcarbamylase; Galactokinase; Arginine; Galactose; Urea cycle

Core tip: Human induced pluripotent stem (hiPS) cells have the potential to differentiate into mature hepatocytes. If undifferentiated hiPS cells persist among transplanted hepatocytes, hiPS cells may potentially develop into cancer. Glucose and arginine are essential for the survival of most cells; however, mature hepatocytes survive in the media because they can produce glucose and arginine using galactokinase and ornithine transcarbamylase, respectively. Therefore, we created a hepatocyte selection medium (HSM) that lacks glucose and arginine but is supplemented with galactose and ornithine. After establishment of co-culture in HSM, human primary hepatocytes survive while hiPS cells die within three days.