miR-100a-5p-enriched exosomes derived from mesenchymal stem cells enhance the anti-oxidant effect in a Parkinson’s disease model via regulation of Nox4/ROS/Nrf2 signaling

Journal of Translational Medicine

Research

Qiongqiong Wang¹  Songzhe He¹  Shaogang Qu²  Yusheng Jason He³  Xiaofang Wang³  Liankuai Chen³ 

[1] Department of Neurology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China;Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515, Guangzhou, Guangdong, China;Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, 510515, Guangzhou, Guangdong, China;Department of Neurology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China;Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515, Guangzhou, Guangdong, China;Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, 510515, Guangzhou, Guangdong, China;Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000, Ganzhou, Jiangxi, China;ImStem Biotechnology, Inc., 400 Farmington Avenue R1808, 06030, Farmington, CT, USA;Zhuhai Hengqin ImStem Biotechnology Co., Ltd, Hengqin New District Huandao Donglu 1889 Building 3, 519000, Zhuhai, Guangdong, China;

关键词: Parkinson's disease;    Dopaminergic neuron;    Mesenchymal stem cell;    Exosomes;    miR-100-5p;    NOX4;   

DOI  :  10.1186/s12967-023-04638-x

 received in 2023-05-24, accepted in 2023-10-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available.MethodsHere, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.g., western blotting, immunofluorescence and immunohistochemistry staining).ResultsWe assessed the levels of DA neuron injury and oxidative stress in MPTP-induced PD mice and MPP+-induced MN9D cells after treating them with T-MSCs or T-MSCs-Exo. Furthermore, T-MSCs-Exo miRNA sequencing analysis revealed that miR-100-5p-enriched T-MSCs-Exo directly targeted the 3′ UTR of NOX4, which could protect against the loss of DA neurons, maintain nigro-striatal system function, ameliorate motor deficits, and reduce oxidative stress via the Nox4-ROS-Nrf2 axis in PD models.ConclusionsThe study suggests that miR-100-5p-enriched T-MSCs-Exo may be a promising biological agent for the treatment of PD.Graphical AbstractSchematic summary of the mechanism underlying the neuroprotective actions of T-MSCs-Exo in PD. T-MSCs Exo may inhibit the expression level of the target gene NOX4 by delivering miR-100-5p, thereby reducing ROS production and alleviating oxidative stress via the Nox4-ROS-Nrf2 axis, thus improving DA neuron damage in PD.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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