Copyright
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Stem cell transplantation and/or adenoviral glial cell line-derived neurotrophic factor promote functional recovery in hemiparkinsonian rats
May-Jywan Tsai, Shih-Chieh Hung, Ching-Feng Weng, Su-Fen Fan, Dann-Ying Liou, Wen-Cheng Huang, Kang-Du Liu, Henrich Cheng
May-Jywan Tsai, Department of Neurosurgery, Neurological Institute, Neurological Institute, Taipei 11217, Taiwan
Shih-Chieh Hung, Department of Medical Research, National Yang Ming University, Institute of Clinical Medicine, Taipei 112, Taiwan
Shih-Chieh Hung, Integrative Stem Cell Center, Department of Orthopaedics, China Medical University Hospital, Taichung 404, Taiwan
Shih-Chieh Hung, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
Shih-Chieh Hung, China Medical University, Graduate Institute of Clinical Medical Sciences, Taichung 404, Taiwan
Shih-Chieh Hung, Department of Medical Research and Education, Taipei Veterans General Hospital, Stem Cell Laboratory, Taipei 112, Taiwan
Ching-Feng Weng, Department of Life Science, Institute of Biotechnology, Haulien 97401, Taiwan
Su-Fen Fan, Dann-Ying Liou, Department of Neurosurgery, Neurological Institute, Taipei 112, Taiwan
Wen-Cheng Huang, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
Kang-Du Liu, Department of neurosurgery, Neurological Institute, Taipei 112, Taiwan
Henrich Cheng, Department of Neurosurgery, Taipei Veterans General Hospital, Center for Neural Regeneration, Neurological Institute, Taipei 112, Taiwan
Author contributions: Liu KD and Cheng H contributed equally to this work; Liu KD and Cheng H coordinated the project, analyzed the data, and edited the manuscript; Tsai MJ and Hung SC conducted cell culture, analyzed the data, and wrote the manuscript; Weng CF, Fan SF, Liou DY, and Huang WC conducted animal studies and performed the research; all authors have read and approved the final manuscript.
Supported by Taipei Veterans General Hospital in Taiwan, No. V106C-012, No. V107C-087, and No. V109C-018; and Ministry of Science and Technology in Taiwan, No. MOST106-2314-B-075-023, No. MOST107-2314-B-010-023, and No. MOST107-2314-B-075-021.
Institutional review board statement: The study was reviewed and approved by the Taipei Veterans General Hospital Institutional Review Board (Approval No. VGHIRB 95-07-23A).
Institutional animal care and use committee statement: The study was reviewed and approved by the Taipei Veterans General Hospital the Animals Committee (No. IACUC 98-061).
Conflict-of-interest statement: None.
Data sharing statement: No additional data are available.
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: Henrich Cheng, MD, PhD, Full Professor, Surgeon, Department of Neurosurgery, Taipei Veterans General Hospital, Center for Neural Regeneration, Neurological Institute, No. 322 Section 2, Shih-Pai Road, Beitou District, Taipei 112, Taiwan. hc_cheng@vghtpe.gov.tw
Received: July 20, 2020
Peer-review started: July 20, 2020
First decision: October 21, 2020
Revised: November 4, 2020
Accepted: November 12, 2020
Article in press: November 12, 2020
Published online: January 26, 2021
ARTICLE HIGHLIGHTS
Research background
Parkinson’s disease (PD) is caused by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Strategies to stop DA degeneration in PD are currently unavailable.
Research motivation
Although levodopa (L-DOPA) treatment is the most common therapy for PD, it becomes less effective after several years and develop severe treatment-related side effects in PD. Devising efficient therapy for PD is urgently needed.
Research objectives
Bone marrow mesenchymal stem cells (BMSCs) are promising tools for PD. BMSCs have a longer therapeutic time window than most pharmacological neuroprotective agents. This study explored the effect of nigral grafts of human BMSCs and overexpressing glial cell line-derived neurotrophic factor (GDNF) in hemiparkinsonian rats.
Research methods
Preinduced human BMSCs (hMSCs) graft or adenoviral (Ad)-GDNF was injected into the SN in a hemiparkinsonian rats.
Research results
Hemiparkinsonian rats that received preinduced hMSC graft and/or Ad-GDNF showed significant recovery of apomorphine-induced rotational behavior and the number of nigral DA neurons.
Research conclusions
Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN.
Research perspectives
Preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.
