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
Abstract
BACKGROUND

Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities.

AIM

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

METHODS

We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms.

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 therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was 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.

CONCLUSION

SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.

Keywords: Autoimmune hepatitis; Stem cells from human exfoliated deciduous teeth; Concanavalin A; Apoptosis; Nuclear factor-kappa B

Core Tip: Autoimmune hepatitis poses an enhancing global burden, underscoring the need to identify novel treatments. To determine the effects of stem cells from human exfoliated deciduous teeth (SHED) on concanavalin A (ConA)-induced autoimmune hepatitis, we pretreated ConA-induced hepatitis mice with SHED. SHED blocked increased expression of alanine aminotransferase and aspartate aminotransferase, and prevented aberrant histopathological liver architecture due to infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. ConA upregulated nuclear factor-kappa B-activated tumor necrosis-alpha and interferon-gamma expression, inducing hepatocyte apoptosis and acute liver injury. SHED administration protected hepatocytes from apoptosis, providing a potential treatment for hepatitis and acute hepatic injury.