Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2020; 12(10): 1196-1213
Published online Oct 26, 2020. doi: 10.4252/wjsc.v12.i10.1196
Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury
Dian-Ri Wang, Yu-Hao Wang, Jian Pan, Wei-Dong Tian
Dian-Ri Wang, Yu-Hao Wang, Jian Pan, Wei-Dong Tian, State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Dian-Ri Wang, Yu-Hao Wang, Jian Pan, Wei-Dong Tian, National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Dian-Ri Wang, Yu-Hao Wang, Jian Pan, Wei-Dong Tian, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Wang DR and Pan J contributed to the conception and design of the study, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; Wang DR performed the in vivo and in vitro experiments; Wang YH participated animal experiments; all authors read and approved the final version of the manuscript.
Supported by the National Key R&D Program of China, No. 2017YFA0104800; the Project of Science & Technology Bureau of Chengdu, No. 2016-HM01-00071-SF; and Sichuan Academic & Technological Leaders Training Support Project.
Institutional review board statement: All experiments involving humans followed the guidelines of the Ethics Committee of West China College of Stomatology.
Institutional animal care and use committee statement: All experiments involved animals were proved by the Ethics Committee of West China College of Stomatology and conducted in accordance with the Ethics Committee guidelines.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request
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 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jian Pan, PhD, Doctor, State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, No. 14 Third Section, Renmin Road South, Chengdu 610041, Sichuan Province, China. jianpancn@scu.edu.cn
Received: May 20, 2020
Peer-review started: May 20, 2020
First decision: June 5, 2019
Revised: June 13, 2020
Accepted: August 16, 2020
Article in press: August 16, 2020
Published online: October 26, 2020
Processing time: 159 Days and 1.2 Hours
Abstract
BACKGROUND

Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair.

AIM

To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery.

METHODS

DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model in vivo and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs.

RESULTS

DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. In vivo, both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls.

CONCLUSION

In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair in vivo. Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.

Keywords: Dental pulp stem cells; Nerve repair; Nerve regeneration; Neurotrophic effects

Core Tip: Dental pulp stem cells (DPSCs) might be an ideal cell source for nerve repair and regeneration for having an inclination to neural differentiation, expressing neurotrophic proteins after induction, and enhancing stem cell proliferation after neural induction. Furthermore, neural induced-DPSCs provided an effective and long-term treatment for crushed nerve with functional recovery and anatomical repair. Thus, DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration. Collectively, our study provided a novel theoretical basis and a promising cell-related therapeutic strategy for peripheral nerve repair and regeneration.