Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2021; 13(1): 78-90
Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.78
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
Abstract
BACKGROUND

Parkinson’s disease (PD) is a neurological disorder characterized by the progressive loss of midbrain dopamine (DA) neurons. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into multiple cell types including neurons and glia. Transplantation of BMSCs is regarded as a potential approach for promoting neural regeneration. Glial cell line-derived neurotrophic factor (GDNF) can induce BMSC differentiation into neuron-like cells. This work evaluated the efficacy of nigral grafts of human BMSCs (hMSCs) and/or adenoviral (Ad) GDNF gene transfer in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.

AIM

To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats.

METHODS

We used immortalized hMSCs, which retain their potential for neuronal differentiation. hMSCs, preinduced hMSCs, or Ad-GDNF effectively enhanced neuronal connections in cultured neurons. In vivo, preinduced hMSCs and/or Ad-GDNF were injected into the substantia nigra (SN) after induction of a unilateral 6-OHDA lesion in the nigrostriatal pathway.

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. However, DA levels in the striatum were not restored by these therapeutic treatments. Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN.

CONCLUSION

The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.

Keywords: Stem cells, Transplantation, Parkinson’s disease, Glial cell line-derived neurotrophic factor, Adenovirus, Neuroregeneration

Core Tip: Strategies to stop neurodegeneration in Parkinson’s disease are currently unavailable. In the present study, transplantation of neurally induced mesenchymal stem cells or overexpressing glial cell line-derived neurotrophic factor to the substantia nigra of hemiparkinsonian rats not only exerted a regenerative effect, but promoted functional restoration. This treatment may have the potential to improve clinical outcome.