ResearchIn-Press PreviewStem cells Open Access | 10.1172/jci.insight.177841
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Chen, J. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Shi, X. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Deng, Y. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Dang, J. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Liu, Y. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Zhao, J. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Rongzhen, L. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Zeng, D. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Wu, W. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Xiong, Y. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Yuan, J. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Chen, Y. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Wang, J. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Lin, W. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Chen, X. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Huang, W. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Olsen, N. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Pan, Y. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Fu, Q. in: JCI | PubMed | Google Scholar
1School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China
4Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
5Division of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
6Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
7School of Veterinary Medicine, Louisiana State University, Baton Rouge, United States of America
8Division of Rheumatology, The Penn State University Hershey Medical Center, Hershey PA, United States of America
9Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
10Otorhinolaryngology, sun yat-sen university, Guangzhou, China
11School of Cell and Gene Therapy, Shanghai Jiaotong University School of Medicine, shanghai, China
Find articles by Zheng, S. in: JCI | PubMed | Google Scholar
Published April 23, 2024 - More info
Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrated that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cells balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of RA patients. Overall, the unique characteristics, including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues, position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.