The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis

Arthritis Research & Therapy

Research

Kanu Goyal¹  William K. Vasileff²  Hisham Awan²  Latha P. Ganesan³  Braden Zeno³  Shane Bruckner³  Wael N. Jarjour³  William L. Willis³  Binnaz Leblebicioglu⁴  Vittoria M. Capria⁵ 

[1] Department of Orthopaedic Surgery, The Ohio State Wexner Medical Center, Hand & Upper Extremity Center, Columbus, OH, USA;Department of Orthopaedics, The Ohio State University, Columbus, OH, USA;Division of Immunology & Rheumatology, The Ohio State University Wexner Medical Center, Columbus, OH, USA;Division of Periodontology, College of Dentistry, The Ohio State University, Columbus, OH, USA;University Laboratory Animal Resources, The Ohio State University, Columbus, OH, USA;

关键词: Rheumatoid arthritis;    Synovial fibroblasts;    Gingival-derived mesenchymal stem cells;    Exosomes;   

DOI  :  10.1186/s13075-023-03185-6

 received in 2023-06-28, accepted in 2023-10-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRheumatoid arthritis is a chronic systemic autoimmune disease that involves transformation of the lining of synovial joints into an invasive and destructive tissue. Synovial fibroblasts become transformed, invading and destroying the bone and cartilage of the affected joint(s). Due to the significant role these cells play in the progression of the disease process, developing a therapeutic strategy to target and inhibit their invasive destructive nature could help patients who are afflicted with this debilitating disease. Gingival-derived mesenchymal stem cells are known to possess immunomodulatory properties and have been studied extensively as potential cell-based therapeutics for several autoimmune disorders.MethodsA chimeric human/mouse model of synovitis was created by surgically implanting SCID mice with a piece of human articular cartilage surrounded by RASF. Mice were injected once with either GMSC or GMSCExo at 5–7 days post-implantation. Histology and IHC were used to assess RASF invasion of the cartilage. Flow cytometry was used to understand the homing ability of GMSC in vivo and the incidence of apoptosis of RASF in vitro.ResultsWe demonstrate that both GMSC and GMSCExo are potent inhibitors of the deleterious effects of RASF. Both treatments were effective in inhibiting the invasive destructive properties of RASF as well as the potential for these cells to migrate to secondary locations and attack the cartilage. GMSC home to the site of the implant and induce programmed cell death of the RASF.ConclusionsOur results indicate that both GMSC and GMSCExo can block the pathological effects of RASF in this chimeric model of RA. A single dose of either GMSC or GMSCExo can inhibit the deleterious effects of RASF. These treatments can also block the invasive migration of the RASF, suggesting that they can inhibit the spread of RA to other joints. Because the gingival tissue is harvested with little difficulty, relatively small amounts of tissue are required to expand the cells, the simple in vitro expansion process, and the increasing technological advances in the production of therapeutic exosomes, we believe that GMSCExo are excellent candidates as a potential therapeutic for RA.

【 授权许可】

CC BY   
© The Author(s) 2023

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