Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2024; 16(2): 191-206
Published online Feb 26, 2024. doi: 10.4252/wjsc.v16.i2.191
Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a
Fan Yang, Wan-Qi Xiong, Chen-Zhi Li, Ming-Jian Wu, Xiu-Zhi Zhang, Chun-Xiao Ran, Zhen-Hao Li, Yan Cui, Bao-Yi Liu, De-Wei Zhao
Fan Yang, Wan-Qi Xiong, Chen-Zhi Li, Ming-Jian Wu, Xiu-Zhi Zhang, Chun-Xiao Ran, Zhen-Hao Li, Yan Cui, Bao-Yi Liu, De-Wei Zhao, Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, China
Author contributions: Liu BY and Zhao DW was the guarantor and designed the study; Yang F and Xiong WQ participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Li CZ, Wu MJ, Zhang XZ, Ran CX, Li ZH, and Cui Y revised the article critically for important intellectual content.
Supported by Project of the National Natural Science Foundation of China, No. 82172398; Key Research Project of the Department of Education of Liaoning Province, No. LJKZZ20220148; Dalian Medical Science Research Project, No. 2111038; and Dalian Dengfeng Plan Medical Key Specialty Construction Project (2021), No. 243.
Institutional animal care and use committee statement: All animal studies were approved by the Animal Welfare and Ethics Committee of the Affiliated Zhongshan Hospital of Dalian University (No. 2022011010).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Yi Liu, PhD, Chief, Professor, Surgeon, Teacher, Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 116001, Liaoning Province, China. liubaoyi-513@163.com
Received: October 26, 2023
Peer-review started: October 26, 2023
First decision: November 9, 2023
Revised: November 18, 2023
Accepted: January 30, 2024
Article in press: January 30, 2024
Published online: February 26, 2024
Processing time: 123 Days and 1.2 Hours
ARTICLE HIGHLIGHTS
Research background

The main focus is understanding knee osteoarthritis (KOA), exploring genetic and biomechanical factors, and investigating the potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) containing miR-29a for early treatment. Key issues include validating safety and efficacy, with resolving these challenges holding significance for advancing effective KOA progression management and future research in the field.

Research motivation

The primary goal of the study is to investigate miR-29a’s role in KOA by creating miR-29a-loaded vesicles and testing their impact in rat models. Achieving this aims to provide insights into early-stage KOA treatment and highlights the potential of extracellular vesicles for future therapeutic interventions in KOA. The significance lies in advancing our understanding of miRNA-based interventions, particularly miR-29a, and paving the way for innovative strategies in the management of KOA progression.

Research objectives

The study involved extracting extracellular vesicles from bone marrow MSCs, engineering vesicles loaded with miR-29a using ultrasonication, and confirming their content through quantitative reverse transcription polymerase chain reaction. In a rat model of KOA, three groups were established and assessed through various analyses, such as behavioral observation, imaging, histological observation, and immunohistochemical detection, offering a comprehensive approach to evaluating arthritis progression. The unique aspect lies in the application of engineered extracellular vesicles for targeted miR-29a delivery in the context of OA treatment.

Research methods

The article explores the multifactorial etiology of KOA, emphasizing the potential of MSC-released extracellular vesicles (exosomes) and microRNAs for cartilage regeneration, signaling a promising avenue for future KOA treatment pending further validation.

Research results

General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis.

Research conclusions

The engineered exosomes loaded with miR-29a attenuate the progression of KOA.

Research perspectives

In future studies, we plan to explore the molecular mechanisms of upstream signaling molecules. We aim to use blood and joint tissue assays to detect inflammation markers, evaluating their influence and elucidating associated mechanisms.