Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease

Zhangxue Wang,1,2,* Chunjuan Yang,3,* Shushan Yan,4,* Jiamei Sun,3,* Jin Zhang,1,2 Zhuojian Qu,5 Wenchang Sun,3 Jie Zang,3 Donghua Xu1– 3 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Rheumatology and Immunology, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 3Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 4Department of Gastrointestinal and Anal Diseases Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 5School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghua Xu; Jie Zang, Email [email protected]; [email protected]: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) are the primary mechanism for the paracrine regulation of MSCs. They deliver proteins, nucleic acids, lipids, and other active compounds to various tissues and organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs and MSC-derived EVs (MSC-EVs) due to their immunomodulatory capabilities, according to mounting data. Since MSC-EVs have low immunogenicity, high stability, and similar biological effects as to MSCs themselves, they are advantageous over cell therapy for potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, systemic sclerosis, Sjogren’s syndrome, and other rheumatoid diseases. This review integrates recent advances in the characteristics, functions, and potential molecular mechanisms of MSC-EVs in rheumatic diseases and provides a new understanding of the pathogenesis of rheumatic diseases and MSC-EV-based treatment strategies.Keywords: mesenchymal stem cells, extracellular vesicles, exosome, immunomodulation, rheumatic disease