Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2025; 17(2): 101395
Published online Feb 26, 2025. doi: 10.4252/wjsc.v17.i2.101395
Exosomal miR-203 from bone marrow stem cells targets the SOCS3/NF-κB pathway to regulate neuroinflammation in temporal lobe epilepsy
Wei Wang, Jian Yin
Wei Wang, Jian Yin, Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Author contributions: Wang W and Yin J conceived the project and jointly wrote the initial draft of the manuscript; Yin J collected and analyzed the data, and provided expert advice and revised the manuscript. All the authors contributed to this study and approved the submitted version.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Second Affiliated Hospital of Dalian Medical University, IACUC protocol number: Protocol No. JL-WW2022120601.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Data sharing statement: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian Yin, PhD, Chief Physician, Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian 116023, Liaoning Province, China. yin_dmu@sina.com
Received: November 28, 2024
Revised: December 27, 2024
Accepted: February 11, 2025
Published online: February 26, 2025
Processing time: 87 Days and 22.6 Hours
Abstract
BACKGROUND

Epilepsy is a prevalent chronic neurological disorder affecting 50 million individuals globally, with temporal lobe epilepsy (TLE) being the most common form. Despite advances in antiepileptic drug development, over 30% of patients suffer from drug-resistant epilepsy, which can lead to severe cognitive impairments and adverse psychosocial outcomes.

AIM

To explore the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal miR-203 in the regulation of neuroinflammation in a mouse model of epilepsy, providing a theoretical basis for the development of targeted microRNA delivery therapies for drug-resistant epilepsy.

METHODS

Adult male C57BL/6 mice were divided into a control group and a TLE model of 30 mice each, and the TLE model group was established by injecting kainic acid. BMSCs were isolated from the mice, and exosomes were purified using ultracentrifugation. Exosomal miR-203 was identified and characterized using high-throughput sequencing and quantitative reverse-transcription polymerase chain reaction. The uptake of exosomes by hippocampal neurons and the subsequent effects on neuroinflammatory markers were assessed using in vitro cell culture models.

RESULTS

Exosomal miR-203 exhibited a significant upregulation in BMSCs derived from epileptic mice. In vitro investigations demonstrated the efficient internalization of these exosomes by hippocampal neurons, resulting in downregulation of suppressor of cytokine signaling 3 expression and activation of the nuclear factor kappaB pathway, ultimately leading to enhanced secretion of pro-inflammatory cytokines.

CONCLUSION

Our study identifies exosomal miR-203 as a key regulator of neuroinflammation in a mouse model of epilepsy. The findings suggest that targeting miR-203 may offer a novel therapeutic strategy for epilepsy by modulating the suppression of cytokine signaling 3/nuclear factor kappaB pathway, thus providing a potential avenue for the development of cell-free therapeutics.

Keywords: Epilepsy; Neuroinflammation; MiR-203; Exosomes; Bone marrow mesenchymal stem cells; Suppressor of cytokine signaling; Nuclear factor kappaB

Core Tip: This study highlights the role of bone marrow mesenchymal stem cell-derived exosomal miR-203 in regulating neuroinflammation in a mouse model of temporal lobe epilepsy. These findings suggest that miR-203 modulates the suppressor of cytokine signaling 3/nuclear factor kappaB pathway, leading to increased neuroinflammation. This pathway activation promotes the secretion of proinflammatory cytokines, contributing to the pathology of epilepsy. Targeting miR-203 may offer a novel therapeutic approach for drug-resistant epilepsy by reducing neuroinflammation and improving patient outcomes, offering potential for future cell-free therapeutic strategies.