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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2019; 11(2): 55-72
Published online Feb 26, 2019. doi: 10.4252/wjsc.v11.i2.55
Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders
Qiang Liu, Mo-Xian Chen, Lin Sun, Chloe U Wallis, Jian-Song Zhou, Li-Juan Ao, Qi Li, Pak C Sham
Qiang Liu, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
Mo-Xian Chen, Li-Juan Ao, School of Rehabilitation, Kunming Medical University, Kunming 650500, Yunnan Province, China
Lin Sun, Department of Psychology, Weifang Medical University, Weifang 261053, Shandong Province, China
Chloe U Wallis, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom
Jian-Song Zhou, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Qi Li, Pak C Sham, Department of Psychiatry, the University of Hong Kong, Hong Kong, China
Pak C Sham, State Key Laboratory of Brain and Cognitive Sciences, Center for Genomic Sciences, the University of Hong Kong, Hong Kong, China
Author contributions: Liu Q and Chen MX contributed equally to this work; Liu Q, Chen MX, Li Q, Ao LJ, and Sham PC designed the research; Liu Q and Chen MX wrote the first draft of the article; Lin S, Zhou JS, and Wallis CU designed the tables and figures; Li Q and Wallis CU revised the draft; Ao LJ and Sham PC contributed to the funding support to this research.
Supported by National Nature Science Foundation of China, No. 81660381
Conflict-of-interest statement: All authors have no conflicts of interest to report.
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: Qi Li, PhD, Postdoctoral Fellow, Department of Psychiatry, the University of Hong Kong, 21 Sasson Roads, Pokfulam, Hong Kong, China. liqihku@gmail.com
Telephone: +852-39719588
Received: October 9, 2018
Peer-review started: October 10, 2018
First decision: November 27, 2018
Revised: December 30, 2018
Accepted: January 22, 2019
Article in press: January 23, 2019
Published online: February 26, 2019
Processing time: 140 Days and 3 Hours
Abstract

Autism and autism spectrum disorders (ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD. Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review will focus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

Keywords: Autism spectrum disorders; Mesenchymal stem cells; Major histocompatibility complex; Inflammation; Maternal immune activation; Cell therapy

Core tip: Autism spectrum disorder (ASD) is a complex, behaviorally defined disorder characterized by severe impairments in social communication and repetitive behavior. Because of an incomplete understanding of the pathology of ASD, available treatment options in ASD are only symptomatic. We discuss the role of immune dysfunction in the etiology of ASD and function of mesenchymal stem cells. We summarize the pre-clinical and clinical evidence for mesenchymal stem cell therapy in ASD and suggest that more basic experiments are needed to better understand the therapeutic mechanisms of mesenchymal stem cells in ASD.