Document Type
Journal Article
Publication Title
World Journal of Stem Cells
Volume
13
Issue
3
First Page
193
Last Page
207
Publisher
Baishideng Publishing Group
School
School of Medical and Health Sciences
RAS ID
38919
Funders
National Natural Science Foundation of China Natural Science Foundation of Fujian Province Xiamen Research Foundation for Science and Technology Project Scientific Research Foundation for Advanced Talents Xiang'an Hospital of Xiamen University
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by the specific destruction of pancreatic islet β cells and is characterized as the absolute insufficiency of insulin secretion. Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications. Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM. However, it is restricted by many factors such as severe shortage of donor sources, progressive loss of donor cells, high cost, etc. As pluripotent stem cells have the potential to give rise to all cells including islet β cells in the body, stem cell therapy for diabetes has attracted great attention in the academic community and the general public. Transplantation of islet β-like cells differentiated from human pluripotent stem cells (hPSCs) has the potential to be an excellent alternative to islet transplantation. In stem cell therapy, obtaining β cells with complete insulin secretion in vitro is crucial. However, after much research, it has been found that the β-like cells obtained by in vitro differentiation still have many defects, including lack of adult-type glucose stimulated insulin secretion, and multi-hormonal secretion, suggesting that in vitro culture does not allows for obtaining fully mature β-like cells for transplantation. A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human islet β cells. Furthermore, PDX1, NKX6.1, SOX9, NGN3, PAX4, etc., are important in inducing hPSC differentiation in vitro. The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functional β-like cells in vitro. This article reviews β cell maturation in vivo and in vitro and the vital roles of key molecules in this process, in order to explore the current problems in stem cell therapy for diabetes.
DOI
10.4252/wjsc.v13.i3.193
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Comments
Sun, Z. Y., Yu, T. Y., Jiang, F. X., & Wang, W. (2021). Functional maturation of immature β cells: A roadblock for stem cell therapy for type 1 diabetes. World Journal of Stem Cells, 13(3), 193-207. https://doi.org/10.4252/wjsc.v13.i3.193