Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2020; 12(8): 752-760
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.752
Practical choice for robust and efficient differentiation of human pluripotent stem cells
Mei Fang, Li-Ping Liu, Hang Zhou, Yu-Mei Li, Yun-Wen Zheng
Mei Fang, Li-Ping Liu, Hang Zhou, Yu-Mei Li, Yun-Wen Zheng, Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Yun-Wen Zheng, School of Biotechnology and Heath Sciences, Wuyi University, Jiangmen 529020, Guangdong Province, China
Yun-Wen Zheng, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki 305-8575, Japan
Yun-Wen Zheng, Yokohama City University School of Medicine, Yokohama, Kanagawa 234-0006, Japan
Yun-Wen Zheng, Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan
Author contributions: Fang M, Liu LP, and Zheng YW designed the study; Fang M drafted the manuscript; Zheng YW, Li YM, Liu LP, and Zhou H contributed to reviewing and revising the manuscript; all authors approved the final manuscript; Fang M and Liu LP contributed equally to this work; Li YM and Zheng YW are senior authors and co-correspondents of this work.
Supported by National Natural Science Foundation of China, No. 81770621; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 18H02866; Natural Science Foundation of Jiangsu Province, No. BK20180281.
Conflict-of-interest statement: The authors declare no potential financial interests.
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, University of Tsukuba Faculty of Medicine, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
Received: March 28, 2020
Peer-review started: March 28, 2020
First decision: April 22, 2020
Revised: April 30, 2020
Accepted: July 1, 2020
Article in press: July 1, 2020
Published online: August 26, 2020

Human pluripotent stem cells (hPSCs) have the distinct advantage of being able to differentiate into cells of all three germ layers. Target cells or tissues derived from hPSCs have many uses such as drug screening, disease modeling, and transplantation therapy. There are currently a wide variety of differentiation methods available. However, most of the existing differentiation methods are unreliable, with uneven differentiation efficiency and poor reproducibility. At the same time, it is difficult to choose the optimal method when faced with so many differentiation schemes, and it is time-consuming and costly to explore a new differentiation approach. Thus, it is critical to design a robust and efficient method of differentiation. In this review article, we summarize a comprehensive approach in which hPSCs are differentiated into target cells or organoids including brain, liver, blood, melanocytes, and mesenchymal cells. This was accomplished by employing an embryoid body-based three-dimensional (3D) suspension culture system with multiple cells co-cultured. The method has high stable differentiation efficiency compared to the conventional 2D culture and can meet the requirements of clinical application. Additionally, ex vivo co-culture models might be able to constitute organoids that are highly similar or mimic human organs for potential organ transplantation in the future.

Keywords: Human pluripotent stem cells, Three dimensional, Embryoid body, Differentiation, Efficient, Three germ layers

Core tip: Identifying a practical way to efficiently differentiate pluripotent stem cells is essential in regenerative medicine. After considering the advantages and limitations of current approaches, we summarize the ideal conditions and systems. We also provide potential choices for efficiently and robustly differentiating human pluripotent stem cells into target cells and tissues in different germ layers.