Human gingiva-derived mesenchymal stem cells ameliorate rheumatoid arthritis through directly targeting of rheumatoid arthritis synovial fibroblasts

Abstract

Abstract Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. The aim of this study is to evaluate whether human gingiva derived MSCs (GMSCs) can alleviate rheumatoid arthritis through directly targeting of rheumatoid arthritis synovial fibroblasts (RA-SF) and underlying mechanism(s). GMSCs or Primary Dermal Fibroblast (PDF) were co-cultured with LPS-stimulated RA-SF. The proliferation, migration and invasion abilities of RA-SF or GMSCs treated RA-SF were examined for determining the suppressive effects of GMSCs on RA-SF. To learn whether GMSCs suppress RA-SF migration and invasion in vivo, GMSCs were subcutaneously co-transplanted with RA-SF and health cartilage into SCID mice to develop a humanized synovitis model, H&E or immunofluorescence staining were employed to determine the effects. Moreover, GMSCs were transferred into collagen induced arthritis model (CIA), proliferation, migration and invasion capacities of synovial fibroblasts from model mice or GMSCs treated mice were compared. We found that the proliferation, migration and invasion capacities of GMSCs treated RA SF were significantly declined. Importantly, the expression of IL-6, IL-8, MMP1, MMP2, MMP3 and MMP13 were dramatically reduced in GMSCs treated RA-SF (qPCR results). Administration of GMSCs was therapeutic in collagen induced arthritis synovial fibroblasts pathology (proliferation, migration and invasion). Furthermore, GMSCs directly suppress RA-SF invasion in a humanized synovitis model. We conclude that the manipulation of GMSCs can ameliorate rheumatoid arthritis (RA) through directly targeting of rheumatoid arthritis synovial fibroblasts.