CD146(+) mesenchymal stem cells display greater therapeutic potential than CD146(–) cells for treating collagen-induced arthritis in mice

BACKGROUND: The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146(+) and CD146(–) MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated. METHODS: Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146(+) and CD146(–) MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA). RESULTS: Compared with CD146(–) MSCs, CD146(+) MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146(–) cells but not when exposed to CD146(+) cells both in vitro and in vivo. IA injection of CD146(+) MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A(+) CD146(+) cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression. CONCLUSIONS: This study suggests that CD146(+) cells have greater potency than CD146(–) cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146(+) cells in treating inflammatory arthritis.