Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1623-1639
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1623
Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis
Yi-Kun Zhou, Ling-Su Zhu, Hua-Ming Huang, Sheng-Jie Cui, Ting Zhang, Yan-Heng Zhou, Rui-Li Yang
Yi-Kun Zhou, Hua-Ming Huang, Sheng-Jie Cui, Ting Zhang, Yan-Heng Zhou, Rui-Li Yang, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
Ling-Su Zhu, Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Zhou YK, Yang RL, Zhu LS, and Zhou YH designed the research study; Zhou YK, Yang RL, Zhu LS, and Huang HM performed the research; Cui SJ and Zhang T contributed new reagents and analytic tools; Zhou YK and Yang RL analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by The National Natural Science Foundation of China, No. 81970940 and No. 81600865; Beijing Natural Science Foundation, No. 7182182; and the National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2018ZX10302207.
Institutional animal care and use committee statement: This study was approved by the Animal Care and Use Committee of the Health Science Center, Peking University (No. 2015-186).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Data are available upon reasonable request from R L Yang at ruiliyangabc@163.com
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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 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: Rui-Li Yang, DDS, PhD, Assistant Professor, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, No. 22 Zhongguancun South Avenue, Beijing 100081, China. ruiliyangabc@163.com
Received: May 31, 2020
Peer-review started: May 31, 2020
First decision: August 22, 2020
Revised: September 20, 2020
Accepted: October 12, 2020
Article in press: October 12, 2020
Published online: December 26, 2020
Processing time: 210 Days and 1.6 Hours
ARTICLE HIGHLIGHTS
Research background

Autoimmune hepatitis (AIH) is a serious autoimmune liver disease that threatens human health globally, thus emphasizing the need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to non-invasively obtain, showed pronounced proliferative and immunomodulatory capacities.

Research motivation

AIH treatment requires long-term or even lifelong use of immunosuppressants, which may cause serious side effects. Some patients are insensitive to treatment and cannot be well controlled. More appropriate and effective medical technologies to cure diabetes are needed. Mesenchymal stem cell infusion could alleviate a variety of diseases such as AIH. SHED show more pronounced proliferative and im-munomodulatory capacities compared to bone marrow mesenchymal stem cells, and can differentiate into hepatocytes in vitro. Non-traumatically collected stem cells (SHED) may therefore be a promising option for treating AIH.

Research objectives

To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms.

Research methods

We used a ConA-induced acute hepatitis mouse model (6–week-old to 8-week-old male Balb/c mice) and an in vitro co-culture system to study the protective effects of SHED on ConA-induced AIH, as well as the underlying mechanisms. Protocols were approved by the Animal Care and Use Committee of the Health Science Center, Peking University (No. 2015-186).

Research results

SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could block the ConA-induced elevation of alanine aminotransferase and aspartate aminotransferase. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which were activated by the nuclear factor-kappa B pathway, to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis.

Research conclusions

We demonstrate that SHED exhibits protective effects in a ConA-induced AIH mouse model. SHED treatment could inhibit the activation of Th1 cells, and reduce the secretion of tumor necrosis-alpha and interferon-gamma expression to inhibit ConA-induced nuclear factor-kappa B pathway activation. This reduces both hepatocyte apoptosis and inflammatory liver damage.

Research perspectives

These results could provide a potential prevention and therapeutic strategy for hepatitis and acute hepatic injury.