Clinical-grade human dental pulp stem cells suppressed the activation of osteoarthritic macrophages and attenuated cartilaginous damage in a rabbit osteoarthritis model

作者：Peilin Li, Yuxing Wang, Zhidong Zhao, Zhiling Li, Jia-Wu Liang, Qian Wang, Bo-Feng Yin, Rui-Cong Hao, Meng-Yue Han, Li Ding, Chu-Tse Wu, Heng Zhu · 发表于：Stem Cell Research & Therapy · 年份：2021 · DOI：10.1186/s13287-021-02353-2 · 被引用次数：47 · 研究领域：Osteoarthritis Treatment and Mechanisms、Mesenchymal stem cell research、Wound Healing and Treatments

BACKGROUND: Although increasing evidence has demonstrated that human dental pulp stem cells (hDPSCs) are efficacious for the clinical treatment of skeletal disorders, the underlying mechanisms remain incompletely understood. Osteoarthritis (OA) is one of the most common degenerative disorders in joints and is characterized by gradual and irreversible cartilaginous tissue damage. Notably, immune factors were newly identified to be closely related to OA development. In this study, we explored the modulatory effects of clinical-grade hDPSCs on osteoarthritic macrophages and their protective effects on cartilaginous tissues in OA joints. METHODS: The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages were explored by phase contrast microscope, transmission electron microscopy, immunostaining, flow cytometry, quantitative polymerase chain reaction, and enzyme linked immunosorbent assay, respectively. Additionally, the factors and signaling pathways that suppressed macrophage activation by hDPSCs were determined by enzyme-linked immunosorbent assay and western-blotting. Furthermore, hDPSCs were administered to a rabbit knee OA model via intra-articular injection. Macrophage activation in vivo and cartilaginous tissue damage were also evaluated by pathological analysis. RESULTS: We found that hDPSCs markedly inhibited osteoarthritic macrophage activation in vitro. The cell morphology, immunophenotype, and inflammatory factor expression...