Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2018; 10(12): 196-211
Published online Dec 26, 2018. doi: 10.4252/wjsc.v10.i12.196
Functional and molecular mechanism of intracellular pH regulation in human inducible pluripotent stem cells
Shih-Chi Chao, Gwo-Jang Wu, Shu-Fu Huang, Niann-Tzyy Dai, Hsu-Kai Huang, Mei-Fang Chou, Yi-Ting Tsai, Shiao-Pieng Lee, Shih-Hurng Loh
Shih-Chi Chao, Shih-Hurng Loh, Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan
Gwo-Jang Wu, Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
Shu-Fu Huang, Mei-Fang Chou, Shih-Hurng Loh, Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
Niann-Tzyy Dai, Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
Hsu-Kai Huang, Division of Chest Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
Yi-Ting Tsai, Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan
Yi-Ting Tsai, Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
Shiao-Pieng Lee, Division of Oral and Maxillofacial Surgery, Department of Dentistry, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan
Shih-Hurng Loh, Department of Pharmacology, National Defense Medical Center, Taipei 11490, Taiwan
Author contributions: Chao SC and Loh SH performed the majority of experiments and analyzed the data; Chao SC, Wu GJ, Dai NT and Loh SH performed conception and design; Wu GJ, Dai NT and Loh SH participated equally in iPSC treatment and providing; Chao SC, Wu GJ, Huang SF, Dai NT, Huang SK, Tsai YT, Lee SP and Loh SH coordinated and interpreted the research; Cha SC and Loh SH wrote the paper; Cha SC, Wu GJ, Huang SF and Loh SH drafted the article or making critical revisions related to important intellectual content of the manuscript; Loh SH final approval of the version of the article to be published.
Supported by Ministry of Science and Technology Grants of Taiwan, No. MOST 106-2320-B-016-003-MY2 (to Loh SH) and No. MOST 106-2314-B-016-037-MY3 (to Tsai YT); National Defense Medical Center Grants of Taiwan, No. MAB-106-033 (to Loh SH), No. MAB-105-043 and No. MAB-106-034 (to Dai NZ); Teh-Tzer Study Group for Human Medical Research Foundation of Taiwan, No. A1061037 and No. A1061054 (to Loh SH).
Institutional review board statement: The manuscript is approved by Institutional Review Board of Tri-Service General Hospital.
Conflict-of-interest statement: All authors declare no potential conflict of interest.
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 to: Shih-Hurng Loh, DPhil, Director, Full Professor, Department of Pharmacology, and Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Taipei 11490, Taiwan. shloh@ndmctsgh.edu.tw
Telephone: +886-2-87924861 Fax: +886-2-87924861
Received: October 17, 2018
Peer-review started: October 17, 2018
First decision: October 26, 2018
Revised: November 14, 2018
Accepted: December 4, 2018
Article in press: December 5, 2018
Published online: December 26, 2018
Core Tip

Core tip: For the first time, we established a model of the intracellular pH (pHi) regulation mechanism in human induced pluripotent stem cells (hiPSCs). The steady-state pHi value of hiPSCs was 7.50-7.68, which greater than that of normal adult cells. The Na+-H+ exchanger, the Na+-HCO3- cotransporter and vacuolar-ATPase were the main acid extruders, while the Cl--HCO3- anion exchanger and the Cl--OH- exchanger were the main acid loaders. Moreover, the pHi and acid-extruding mechanism were decreased during the loss of pluripotency in hiPSCs. pHi regulators represent an attractive target for differentiation efficiency or culture quality.