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World J Stem Cells. Apr 26, 2023; 15(4): 182-195
Published online Apr 26, 2023. doi: 10.4252/wjsc.v15.i4.182
Human pluripotent stem cell-derived β cells: Truly immature islet β cells for type 1 diabetes therapy?
Helen Jiang, Fang-Xu Jiang
Helen Jiang, Sir Charles Gairdner Hospital, University of Western Australia, Perth 6009, Australia
Fang-Xu Jiang, School of Biomedical Sciences, University of Western Australia, Perth 6009, Australia
Fang-Xu Jiang, School of Health and Medical Sciences, Edith Cowan University, Perth 6027, Australia
Author contributions: Jiang H wrote the first draft of the manuscript; Jiang FX conceived and designed the research; and all authors have edited, revised, reviewed and approved submission of the manuscript.
Supported by the Juvenile Diabetes Research Foundation, No. 4-2006-1025; Diabetes Australia Research Trust; and Telethon Perth Children’s Hospital Research Fund (TPCHRF) grant to Jiang FX.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fang-Xu Jiang, PhD, Adjunct Associate Professor, School of Biomedical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley WA 6009, Perth 6009, Australia. fang-xu.jiang@perkins.uwa.edu.au
Received: December 27, 2022
Peer-review started: December 27, 2022
First decision: January 6, 2023
Revised: January 30, 2023
Accepted: March 20, 2023
Article in press: March 20, 2023
Published online: April 26, 2023
Abstract

A century has passed since the Nobel Prize winning discovery of insulin, which still remains the mainstay treatment for type 1 diabetes mellitus (T1DM) to this day. True to the words of its discoverer Sir Frederick Banting, “insulin is not a cure for diabetes, it is a treatment”, millions of people with T1DM are dependent on daily insulin medications for life. Clinical donor islet transplantation has proven that T1DM is curable, however due to profound shortages of donor islets, it is not a mainstream treatment option for T1DM. Human pluripotent stem cell derived insulin-secreting cells, pervasively known as stem cell-derived β cells (SC-β cells), are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy. Here we briefly review how islet β cells develop and mature in vivo and several types of reported SC-β cells produced using different ex vivo protocols in the last decade. Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown, the SC-β cells have not been directly compared to their in vivo counterparts, generally have limited glucose response, and are not yet fully matured. Due to the presence of extra-pancreatic insulin-expressing cells, and ethical and technological issues, further clarification of the true nature of these SC-β cells is required.

Keywords: Human pluripotent stem cells, Stem cell-derived β cells, Islet β cells, Type 1 diabetes mellitus, Cell replacement therapy

Core Tip: Diabetes mellitus (DM) is a metabolic condition of absolute or relative deficiency in insulin. Since the discovery of insulin 100 years ago, there has been slow progress in the treatment of type 1 DM (T1DM) in clinical practice. In the scientific community however, there is much interest and progression in the research of human pluripotent stem cell derived insulin producing β-like cells, pervasively known as stem cell-derived β cells (SC-β cells). If they are determined to be genuine, scalable and functionally matured, SC-β cells have the potential to cure T1DM through cell replacement therapy.