Immunomodulatory, anti-synoviocyte, and anti-osteoclastic abilities of embryonic stem cell-derived mesenchymal stem cells in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, fibroblast-like synoviocyte hyperactivation, and osteoclast-mediated bone destruction. Mesenchymal stem cells (MSCs) derived from adult tissues exhibit therapeutic potential owing to their regenerative and immunomodulatory properties; However, commercialization remains challenging due to limitations in large-scale production with consistent quality. Contrastingly, MSCs derived from embryonic stem cells can be continuously produced and exhibit minimal variation, with high biological and genetic uniformity. We confirmed that DW-MSCs exhibit MSC characteristics, including proliferative capacity, surface marker expression, and immunomodulatory function in vitro, by comparison with umbilical cord-derived MSCs (UC-MSCs) as one representative type of adult tissue-derived MSCs. We further evaluated their effects on RA pathology via in vitro assays of FLS migration and osteoclastogenesis. Although DW-MSCs showed lower immunosuppressive capacity than UC-MSCs, DW-MSCs retained functional immunosuppressive efficacy and exhibited superior inhibition of FLS migration and osteoclastogenesis, both of which are critical in the complex pathogenesis of RA. In a collagen-induced arthritis mouse model, intra-articular injection of DW-MSCs reduced inflammation and bone erosion, with an increased regulatory T cell/T-helper-17 ratio in draining lymph nodes. These findings demonstrated the therapeutic potential of DW-MSCs and support their application as a scalable and standardized stem cell-based treatment for RA.