Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Efficacy of extracellular vesicles derived from mesenchymal stromal cells in regulating senescence: In vitro and in vivo insights
Shuang-Shuang Yang, Si-Yu Chen, Wen-Ya Zhuang, Jing Han, Ya Liu, Li Deng, Hui-Zhen Guo, He-Ran Ma, Yi Tan
Shuang-Shuang Yang, Si-Yu Chen, Wen-Ya Zhuang, Jing Han, Hui-Zhen Guo, He-Ran Ma, Yi Tan, Department of Research and Development, Qilu Cell Therapy Technology Co. Ltd., Jinan 250100, Shandong Province, China
Ya Liu, College of Marine Life Science, Ocean University of China, Qingdao 266003, Shandong Province, China
Li Deng, Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250013, Shandong Province, China
Li Deng, Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Jinan 250013, Shandong Province, China
Yi Tan, Department of Research and Development, Shandong Yinfeng Life Science Research Institute, Jinan 250100, Shandong Province, China
Author contributions: Yang SS contributed to the conceptualization, methodology, and original draft writing; Chen SY contributed to the data analysis and review, editing, and writing of the manuscript; Deng L contributed to the investigation; Zhuang WY and Han J contributed software; Guo HZ contributed to the formal analysis; Ma HR was responsible for the supervision; Liu Y and Tan Y were responsible for the project administration and funding acquisition. All the authors have read and approved the final manuscript.
Supported by the Ministry of Science and Technology of China, No. 2021YFA1101502.
Institutional review board statement: The study was approved by the Medical Ethics Committee of Yantai Yuhuangding Hospital, China, Approval No.[2021]003.
Institutional animal care and use committee statement: The research was performed in alignment with the guidelines set forth in the “Guide for the Care and Use of Laboratory Animals” as published by the United States National Institutes of Health (NIH publication No. 85-23, revised 2011) and received approval from the Scientific Ethics Special Committee of the Academic Committee of Ocean University of China (Approval No. OUC-AE-2022-162).
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: All data are available with the corresponding author upon reasonable request.
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: Yi Tan, PhD, Department of Research and Development, Qilu Cell Therapy Technology Co. Ltd., No. 6 Gangyuan Road, Jinan 250100, Shandong Province, China.
pkuty@126.com
Received: June 10, 2025
Revised: July 1, 2025
Accepted: September 8, 2025
Published online: October 26, 2025
Processing time: 140 Days and 18.8 Hours
BACKGROUND
Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) can be used for anti-aging therapy and treating various aging-related diseases. However, the clinical application of MSC-EVs is still limited, mainly due to insufficient information on the preparation process, quality, and mechanism of action of MSC-EVs.
AIM
To study the biological effects of MSC-EVs in regulating cellular senescence.
METHODS
In this study, we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use. To support the clinical use of our product as a therapeutic agent, we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.
RESULTS
The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associated β-galactosidase, matrix metallopeptidase 1, P21, and interleukin-1β and increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts. Similarly, treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice, aging-related histopathological changes, oxidative stress, and aging-related gene expression.
CONCLUSION
These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism. Overall, these findings strongly suggest that MSC-EVs hold promise for aging therapy.
Core Tip: This study addresses the practical challenges of using mesenchymal stromal cell-derived extracellular vesicles (EVs) for anti-aging therapy. We developed a scalable production method and quality control standards for clinical use. Tests in cells and animals have shown that these EVs effectively decrease the expression of aging markers, repair age-related damage, reduce oxidative stress, and normalize gene activity. The key mechanisms involved in fighting oxidative stress and fine-tuning metabolism. These findings position EVs as promising, ready-to-use anti-aging treatments.
