Gingival mesenchymal stem cells derived from patients with rheumatoid arthritis treat experimental arthritis

作者：Yuluan Hou, Ximei Zhang, Donglan Zeng, Shangling Zhu, Yang Luo, Junlong Dang, Wenbin Wu, Yiding Xiong, Jun Zhao, Jianlin Huang, Jia Yuan, Shuhong Wang, Julie Wang, Hanshi Xu, Wei Zhang, Hong Ai, Zheng Chen, Song Guo Zheng · 发表于：Open Research (University of Surrey) · 年份：2024 · DOI：10.1002/viw.20240021 · 被引用次数：2 · 研究领域：Mesenchymal stem cell research、Periodontal Regeneration and Treatments、Osteoarthritis Treatment and Mechanisms

Abstract A therapeutic strategy using mesenchymal stem cells (MSCs) has been accepted as a novel therapy for treating rheumatoid arthritis (RA). Human gingiva‐derived MSCs (GMSCs) are superior in regulating immune responses. Autologous MSCs are the optimal candidate to avoid the potential risks of allogenic MSCs. However, whether autologous GMSCs from RA patients are therapeutic remains unknown. In this study, we compared the therapeutic efficacy of GMSCs derived from patients with RA (RA‐GMSCs) and that from health donors (H‐GMSCs) in vivo and in vitro. Then, we utilized RNA‐sequencing, the molecular and cellular assays to determine the immunomodulatory molecules that contribute to the therapeutic effect of RA‐GMSCs on both collagen‐induced arthritis (CIA) and humanized synovitis models. We demonstrated that GMSCs derived from patients with RA (RA‐GMSCs) and health donors (H‐GMSCs) shared a similar expression of immunomodulatory molecules. Moreover, RA‐GMSCs were as effective as H‐GMSCs in suppressing T‐cell proliferation, proinflammatory cytokines secretion, as well as osteoclast differentiation in vitro. In addition, RA‐GMSCs had a robust therapeutic effect on the CIA model. Importantly, RA GMSCs can survive for at least 24 days in a CIA mouse model and can be distributed in the spleen, lymph nodes, and joints. Specifically, RA‐GMSCs decreased the frequency of Th1 and Th17 cells whereas enhanced Treg cells, reducing the joint histopathological scores of lymphocytes, osteoc...