Department of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan, R.O.C.
College of General Studies, Yuan Ze University, Taoyuan City, Taiwan, R.O.C.
PLoS One. 2018 Nov 21;13(11):e0205563. doi: 10.1371/journal.pone.0205563. eCollection 2018.
Osteoarthritis (OA), one of the most common joint disease, affects more than 80% of the population aged 70 or over. Mesenchymal stem cells (MSCs) show multi-potent differentiation and self-renewal capability, and, after exposure to an inflammatory environment, also exhibit immunosuppressive properties. In this study, we have used a model of lipopolysaccharide (LPS)-stimulated chondrocytes to evaluate MSC anti-inflammatory efficacy. The anti-inflammatory mechanism was tested in two cell-contained culture systems: (i) MSC-chondrocyte indirect contact system and (ii) MSC-chondrocyte direct contact system, and one cytokine-only culture system: MSC-conditioned medium (CM) system. Results showed that MSCs reduced chondrocyte inflammation through both paracrine secretion and cell-to-cell contact. The inflammation-associated, and free-radical-related genes were down-regulated significantly in the direct contact system on 24 h, however, the TNF-α. IL-6 were upregulated and aggrecan, COLII were downregulated on 72 h in direct contact system. Moreover, we found CM produced by MSC possess well therapeutic effect on inflammatory chondorcyte, and the 10-fold concentrated MSC-conditioned medium could down-regulated chondorcyte synthesis inflammation-associated, and free-radical-related genes, such as TNF-α, IL-1β, IL-6 and iNOS even treated for 72 h. In conclusion, MSC-CM showed great potential for MSC-based therapy for OA.
骨关节炎（OA）是最常见的关节疾病之一，影响着 80%以上 70 岁或以上的人群。间充质干细胞（MSCs）具有多向分化和自我更新能力，在暴露于炎症环境后，还表现出免疫抑制特性。在这项研究中，我们使用脂多糖（LPS）刺激的软骨细胞模型来评估 MSC 的抗炎疗效。在两种细胞包含的培养系统中测试了抗炎机制：（i）MSC-软骨细胞间接接触系统和（ii）MSC-软骨细胞直接接触系统，以及一种仅细胞因子培养系统：MSC 条件培养基（CM）系统。结果表明，MSCs 通过旁分泌和细胞间接触减少软骨细胞炎症。在直接接触系统中，炎症相关和自由基相关基因在 24 小时内显著下调，但在直接接触系统中，TNF-α、IL-6 在 72 小时内上调，聚集蛋白聚糖、COLII 在 72 小时内下调。此外，我们发现 MSC 产生的 CM 对炎症性软骨细胞具有良好的治疗作用，10 倍浓缩的 MSC 条件培养基可下调软骨细胞合成炎症相关和自由基相关基因，如 TNF-α、IL-1β、IL-6 和 iNOS，甚至在 72 小时后仍有治疗作用。总之，MSC-CM 为 OA 的 MSC 治疗提供了巨大潜力。
