Abstract
BackgroundThe 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.MethodsFlow 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).ResultsCompared 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.ConclusionsThis 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.
Highlights
The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown
There was a significant difference in growth rate between HUCSCs and Melanoma cell adhesion molecule (CD146)+ cells after 4 hours of culture (Fig. 1c; 5 × 103 cells, P ≤0.001)
Our study shows that CD146+ cells tended to suppress arthritis progression, as shown by their effects on chondrogenesis, IL-6 and IL-17 cytokine expression, and joint histology
Summary
The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. 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). 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.
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