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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2018; 10(11): 146-159
Published online Nov 26, 2018. doi: 10.4252/wjsc.v10.i11.146
Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease
Saifun Nahar, Yoshiki Nakashima, Chika Miyagi-Shiohira, Takao Kinjo, Zensei Toyoda, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi, Jiro Fujita
Saifun Nahar, Jiro Fujita, Department of Infectious, Respiratory, and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Yoshiki Nakashima, Chika Miyagi-Shiohira, Hirofumi Noguchi, Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Takao Kinjo, Zensei Toyoda, Department of Basic Laboratory Sciences, School of Health Sciences in the Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Naoya Kobayashi, Okayama Saidaiji Hospital, Okayama 704-8192, Japan
Issei Saitoh, Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata 951-8514, Japan
Masami Watanabe, Department of Urology, Okayama Univer sity Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
Author contributions: Nahar S, Nakashima Y, Miyagi-Shiohira C and Noguchi H designed and conducted the study; Nahar S, Nakashima Y, Miyagi-Shiohira C, Kinjo T, Toyoda Z and Noguchi H collected, analysed and interpreted the data; Kinjo T, Kobayashi N, Saitoh I, Watanabe M and Fujita J provided the materials; drafting of the manuscript, Nahar S, Nakashima Y and Noguchi H drafted, revised the manuscript; Nahar S, Nakashima Y, Miyagi-Shiohira C, Kinjo T, Toyoda Z, Kobayashi N, Saitoh I, Watanabe M, Noguchi H and Fujita J approved the final version of the manuscript; Nahar S takes responsibility for the integrity of all of the data analyses.
Conflict-of-interest statement: Authors of this manuscript have no conflicts of interest to disclose.
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: Hirofumi Noguchi, MD, PhD, Professor, Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. noguchih@med.u-ryukyu.ac.jp
Telephone: +81-98-8951696 Fax: +81-98-8951684
Received: August 10, 2018
Peer-review started: August 13, 2018
First decision: August 24, 2018
Revised: September 7, 2018
Accepted: October 11, 2018
Article in press: October 12, 2018
Published online: November 26, 2018
Processing time: 108 Days and 3.2 Hours
Abstract

Adipose-derived mesenchymal stem cells (ADSCs) are a treatment cell source for patients with chronic liver injury. ADSCs are characterized by being harvested from the patient’s own subcutaneous adipose tissue, a high cell yield (i.e., reduced immune rejection response), accumulation at a disease nidus, suppression of excessive immune response, production of various growth factors and cytokines, angiogenic effects, anti-apoptotic effects, and control of immune cells via cell-cell interaction. We previously showed that conditioned medium of ADSCs promoted hepatocyte proliferation and improved the liver function in a mouse model of acute liver failure. Furthermore, as found by many other groups, the administration of ADSCs improved liver tissue fibrosis in a mouse model of liver cirrhosis. A comprehensive protein expression analysis by liquid chromatography with tandem mass spectrometry showed that the various cytokines and chemokines produced by ADSCs promote the healing of liver disease. In this review, we examine the ability of expressed protein components of ADSCs to promote healing in cell therapy for liver disease. Previous studies demonstrated that ADSCs are a treatment cell source for patients with chronic liver injury. This review describes the various cytokines and chemokines produced by ADSCs that promote the healing of liver disease.

Keywords: Cell transplantation therapy; Cytokine; Hepatocytes; Liquid chromatography with tandem mass spectrometry; Liver cirrhosis; Adipose-derived mesenchymal stem cells

Core tip: We previously showed that conditioned medium of adipose-derived mesenchymal stem cells (ADSCs) promoted hepatocyte proliferation and improved the liver function in a mouse model of acute liver failure. Furthermore, as reported by many other groups, the administration of ADSCs improved liver tissue fibrosis in a mouse model of liver cirrhosis. A comprehensive protein expression analysis by liquid chromatography with tandem mass spectrometry showed that the various cytokines and chemokines produced by ADSCs have the ability to promote the healing of liver disease. In this review, we examine the ability of the expressed protein components of ADSCs to promote healing in cell therapy for liver disease.