Editorial
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2019; 11(7): 375-382
Published online Jul 26, 2019. doi: 10.4252/wjsc.v11.i7.375
Predicting differentiation potential of human pluripotent stem cells: Possibilities and challenges
Li-Ping Liu, Yun-Wen Zheng
Li-Ping Liu, Yun-Wen Zheng, Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Li-Ping Liu, Yun-Wen Zheng, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki 305-8575, Japan
Yun-Wen Zheng, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Author contributions: Liu LP and Zheng YW conceived the study and drafted the manuscript; both authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 81770621; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 16K15604 and No. 18H02866; and Natural Science Foundation of Jiangsu Province, No. BK20180281.
Conflict-of-interest statement: The authors have no conflict of interest 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/
Corresponding author: Yun-Wen Zheng, PhD, Associate Professor, University of Tsukuba Faculty of Medicine, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. ywzheng@md.tsukuba.ac.jp
Telephone: +81-29-853-3221
Received: May 7, 2019
Peer-review started: May 10, 2019
First decision: June 5, 2019
Revised: June 12, 2019
Accepted: June 20, 2019
Article in press: June 29, 2019
Published online: July 26, 2019
Processing time: 80 Days and 20.5 Hours
Abstract

The capability of human pluripotent stem cell (hPSC) lines to propagate indefinitely and differentiate into derivatives of three embryonic germ layers makes these cells be powerful tools for basic scientific research and promising agents for translational medicine. However, variations in differentiation tendency and efficiency as well as pluripotency maintenance necessitate the selection of hPSC lines for the intended applications to save time and cost. To screen the qualified cell lines and exclude problematic cell lines, their pluripotency must be confirmed initially by traditional methods such as teratoma formation or by high-throughput gene expression profiling assay. Additionally, their differentiation potential, particularly the lineage-specific differentiation propensities of hPSC lines, should be predicted in an early stage. As a complement to the teratoma assay, RNA sequencing data provide a quantitative estimate of the differentiation ability of hPSCs in vivo. Moreover, multiple scorecards have been developed based on selected gene sets for predicting the differentiation potential into three germ layers or the desired cell type many days before terminal differentiation. For clinical application of hPSCs, the malignant potential of the cells must also be evaluated. A combination of histologic examination of teratoma with quantitation of gene expression data derived from teratoma tissue provides safety-related predictive information by detecting immature teratomas, malignancy marker expression, and other parameters. Although various prediction methods are available, distinct limitations remain such as the discordance of results between different assays and requirement of a long time and high labor and cost, restricting their wide applications in routine studies. Therefore, simpler and more rapid detection assays with high specificity and sensitivity that can be used to monitor the status of hPSCs at any time and fewer targeted markers that are more specific for a given desired cell type are urgently needed.

Keywords: Human pluripotent stem cells, Induced pluripotent stem cells, Embryonic stem cells, Differentiation potential, Prediction, Pluripotency, Malignant potential, Embryoid bodies, Lineage-specific differentiation, Teratoma

Core tip: To save time and costs in basic research and clinical application, it is necessary to predict the differentiation potential of human pluripotent stem cell (hPSC) lines. Multiple methods are available for pluripotency screening, lineage-specific differentiation propensity prediction, and malignancy potential detection, which can be used to select hPSCs. However, simpler and quicker methods using fewer specific targeted markers for the desired cell type are urgently required for routine work.