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World J Stem Cells. Aug 26, 2020; 12(8): 761-775
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.761
Human embryonic stem cells as an in vitro model for studying developmental origins of type 2 diabetes
Andy Chun-Hang Chen, Kai Fai Lee, William Shu Biu Yeung, Yin Lau Lee
Andy Chun-Hang Chen, Kai Fai Lee, Yin Lau Lee, Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China
Andy Chun-Hang Chen, Kai Fai Lee, William Shu Biu Yeung, Yin Lau Lee, Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China
Author contributions: Chen ACH and Lee YL conceived the study and drafted the manuscript; Lee KF, Yeung WSB, and Lee YL contributed to critical revision and editing of the manuscript.
Supported by a small project grant from the University of Hong Kong, No. 201409176196.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Yin Lau Lee, PhD, Research Scientist, Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
Received: March 12, 2020
Peer-review started: March 12, 2020
First decision: April 25, 2020
Revised: April 28, 2020
Accepted: June 14, 2020
Article in press: June 14, 2020
Published online: August 26, 2020

The developmental origins of health and diseases (DOHaD) is a concept stating that adverse intrauterine environments contribute to the health risks of offspring. Since the theory emerged more than 30 years ago, many epidemiological and animal studies have confirmed that in utero exposure to environmental insults, including hyperglycemia and chemicals, increased the risk of developing noncommunicable diseases (NCDs). These NCDs include metabolic syndrome, type 2 diabetes, and complications such as diabetic cardiomyopathy. Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development. Embryonic stem cells (ESCs) have also been utilized by researchers to study the DOHaD. ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage; therefore, they are excellent in vitro models for studying early developmental events. More importantly, human ESCs (hESCs) are the best alternative to human embryos for research because of ethical concerns. In this review, we will discuss different maternal conditions associated with DOHaD, focusing on the complications of maternal diabetes. Next, we will review the differentiation protocols developed to generate different cell lineages from hESCs. Additionally, we will review how hESCs are utilized as a model for research into the DOHaD. The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.

Keywords: Development origins of health and diseases, Maternal diabetes, Environmental insults, Type 2 diabetes, Human embryonic stem cells, Epigenetics

Core tip: The study of the mechanisms by which the intrauterine environment regulates offspring health is important. In this review, we will discuss the use of human embryonic stem cells as an in vitro model for understanding the developmental origins of diseases such as type 2 diabetes.