Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2019; 11(9): 705-721
Published online Sep 26, 2019. doi: 10.4252/wjsc.v11.i9.705
Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment
Kinji Furuya, Yun-Wen Zheng, Daisuke Sako, Kenichi Iwasaki, Dong-Xu Zheng, Jian-Yun Ge, Li-Ping Liu, Tomoaki Furuta, Kazunori Akimoto, Hiroya Yagi, Hiromi Hamada, Hiroko Isoda, Tatsuya Oda, Nobuhiro Ohkohchi
Kinji Furuya, Yun-Wen Zheng, Daisuke Sako, Kenichi Iwasaki, Dong-Xu Zheng, Jian-Yun Ge, Li-Ping Liu, Tomoaki Furuta, Tatsuya Oda, Nobuhiro Ohkohchi, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Yun-Wen Zheng, Li-Ping Liu, Institute of Regenerative Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Yun-Wen Zheng, Department of Regenerative Medicine, School of Medicine, Yokohama City University, Yokohama 236-0004, Japan
Daisuke Sako, Kazunori Akimoto, Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan
Hiroya Yagi, Hiromi Hamada, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Hiroko Isoda, Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
Author contributions: Furuya K, Sako D, Iwasaki K, Ge JY, Liu LP and Furuta T performed the experiments; Furuya K, Sako D and Iwasaki K analyzed the data; Zheng DX performed bioinformatics; Akimoto K, Yagi H, Hamada H, Isoda H supplied experimental materials and resources; Ohkohchi N and Zheng YW conceived the study; Furuya K drafted the manuscript; Zheng YW and Oda T contributed to discuss and review the final manuscript; all the authors approved the final manuscript; Furuya K, Zheng YW and Sako D contributed equally to this work.
Supported by National Natural Science Foundation of China, No. 81770621; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 16K15604, No. 18H02866; Japan Science and Technology Agency-Japan International Cooperation Agency's (JST-JICA) Science and Technology Research Partnership for Sustainable Development (SATREPS) Project.
Institutional review board statement: All specimens and cells from the patients were obtained after their informed consent and ethical permission was obtained for participation in the study.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
Data sharing statement: Transcriptome datasets of primary amniotic epithelial cells from the Sequence Read Archive (SRA) of the NCBI are available in the website. SRA number is listed in Table 2. Participants gave informed consent for publication.
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/
Corresponding author: Yun-Wen Zheng, PhD, Associate Professor, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, University of Tsukuba Faculty of Medicine, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. ywzheng@md.tsukuba.ac.jp
Telephone: +81-29-8533221 Fax: +81-29-8533222
Received: February 26, 2019
Peer-review started: February 27, 2019
Revised: August 6, 2019
Accepted: August 27, 2019
Article in press: August 27, 2019
Published online: September 26, 2019
Core Tip

Core tip: Amniotic stem cells were exploited as a cell source alternative to liver transplantation therapy instead of induced pluripotent stem cells. However, they presented with low hepatic function efficiency. We used 3D co-culture and a combination of supportive somatic stem cells to simulate an in vivo microenvironment. Our selected subpopulation of adherent amniotic stem cells self-organized ex vivo and generated functional organoids. Cell selection methods and bioinformatics may help refine the differentiation protocol.