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

Abstract

Abstract Background 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. To avoid the potential risks of allogenic MSC, autologous MSCs are the optimal candidate. However, whether autologous GMSCs from RA patients are therapeutic remains unknown. Methods 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 therapeutic effect of RA-GMSCs on both collagen-induced arthritis (CIA) and humanized synovitis models. Results We demonstrated that GMSCs derived from patients with RA (RA-GMSCs) and that from health donors (H-GMSCs) shared the 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 collagen-induced arthritis (CIA) model. Specifically, RA-GMSCs decreased the frequency of Th1 and Th17 cells whereas enhanced Treg cells, reducing the joint histopathological scores of lymphocytes, osteoclasts and cartilages. Importantly, RA-GMSCs were also effective in suppressing inflamed synoviocytes (RA-FLSs) proliferation, migration and invasion in vitro, and cartilage invasion in a humanized synovitis model in vivo. Conclusion Our study implies that manipulation of RA-GMSCs is therapeutic in CIA mice and humanized synovitis models and may have a therapeutic potential in RA patients using autologous GMSCs in the future. Graphical abstract