Research Paper|Volume 15, Issue 5|pp 1358—1370

Ginkgolide A improves the pleiotropic function and reinforces the neuroprotective effects by mesenchymal stem cell-derived exosomes in 6-OHDA-induced cell model of Parkinson’s disease

William Shao-Tsu Chen^1,², Tzu-Ying Lin³, Chia-Hua Kuo⁴, Dennis Jine-Yuan Hsieh^5,⁶, Wei-Wen Kuo⁷, Shih-Chieh Liao⁸, Hui-Chuan Kao⁹, Da-Tong Ju¹⁰, Yu-Jung Lin³, Chih-Yang Huang^3,^11,^12,^13,¹⁴

¹Department of Psychiatry, Tzu Chi General Hospital, Hualien 97004, Taiwan
²School of Medicine Tzu Chi University, Hualien 97004, Taiwan
³Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
⁴Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
⁵Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan
⁶School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
⁷Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
⁸Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
⁹Department of Public Health, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
¹⁰Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
¹¹Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
¹²Department of Biological Science and Technology, Asia University, Taichung, Taiwan
¹³Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan
¹⁴Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

* Equal contribution

Received: June 14, 2022Accepted: February 11, 2023Published: February 20, 2023

https://doi.org/10.18632/aging.204526

Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Parkinson’s disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal cell death. We investigated the function of Ginkgolide A (GA) to reinforce Wharton’s Jelly-derived mesenchymal stem cells (WJMSCs) for treating the in vitro model of PD. GA enhanced the self-renewal, proliferation, and cell homing function of WJMSCs as assessed by MTT and transwell co-culture assay with a neuroblastoma cell line. GA pre-treated WJMSCs can restore 6-hydroxydopamine (6-OHDA)-induced cell death in a co-culture assay. Furthermore, exosomes isolated from GA pre-treated WJMSCs significantly rescued 6-OHDA-induced cell death as determined by MTT assay, flow cytometry, and TUNEL assay. Western blotting showed that apoptosis-related proteins were decreased following GA-WJMSCs exosomal treatment which further improved mitochondrial dysfunction. We further demonstrated that exosomes isolated from GA-WJMSCs could restore autophagy using immunofluorescence staining and immunoblotting assay. Finally, we used the alpha-synuclein recombinant protein and found that exosomes derived from GA-WJMSCs led to the reduced aggregation of alpha-synuclein compared to that in control. Our results suggested that GA could be a potential candidate for strengthening stem cell and exosome therapy for PD.