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

Abstract

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.