Marsh S, Constantin-Teodosiu T, Chapman V, Sottile V
School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Pain Centre Versus Arthritis, University of Nottingham, Nottingham, United Kingdom.
Front Bioeng Biotechnol. 2022 Jun 22;10:908507. doi: 10.3389/fbioe.2022.908507. eCollection 2022.
The increasing prevalence of joint disease, and in particular osteoarthritis (OA), calls for novel treatment strategies to prevent disease progression in addition to existing approaches focusing mainly on the relief of pain symptoms. The inherent properties of mesenchymal stem cells (MSCs) make them an attractive candidate for novel tissue repair strategies, as these progenitors have the potential to differentiate into chondrocytes needed to replace degraded cartilage and can exert a modulating effect on the inflammatory environment of the diseased joint. However, the inflammatory environment of the joint may affect the ability of these cells to functionally integrate into the host tissue and exert beneficial effects, as hinted by a lack of success seen in clinical trials. Identification of factors and cell signalling pathways that influence MSC function is therefore critical for ensuring their success in the clinic, and here the effects of inflammatory mediators on bone marrow-derived MSCs were evaluated. Human MSCs were cultured in the presence of inflammatory mediators typically associated with OA pathology (IL-1β, IL-8, IL-10). While exposure to these factors did not produce marked effects on MSC proliferation, changes were observed when the mediators were added under differentiating conditions. Results collected over 21 days showed that exposure to IL-1β significantly affected the differentiation response of these cells exposed to chondrogenic and osteogenic conditions, with gene expression analysis indicating changes in MAPK, Wnt and TLR signalling pathways, alongside an increased expression of pro-inflammatory cytokines and cartilage degrading enzymes. These results highlight the value of MSCs as a preclinical model to study OA and provide a basis to define the impact of factors driving OA pathology on the therapeutic potential of MSCs for novel OA treatments.
关节疾病，尤其是骨关节炎（OA）的患病率不断上升，这就需要除了现有的主要侧重于缓解疼痛症状的方法之外，还要有新的治疗策略来预防疾病进展。间充质干细胞（MSCs）的固有特性使其成为新型组织修复策略的有吸引力的候选者，因为这些祖细胞有潜力分化为替代退化软骨所需的软骨细胞，并能对患病关节的炎症环境发挥调节作用。然而，正如临床试验中所见的缺乏成功所暗示的那样，关节的炎症环境可能会影响这些细胞功能整合到宿主组织并发挥有益作用的能力。因此，确定影响MSC功能的因素和细胞信号通路对于确保它们在临床上的成功至关重要，在此评估了炎症介质对骨髓来源的MSCs的影响。人MSCs在通常与OA病理相关的炎症介质（IL-1β、IL-8、IL-10）存在的情况下进行培养。虽然暴露于这些因素对MSC增殖没有产生显著影响，但在分化条件下添加这些介质时观察到了变化。在21天内收集的结果表明，暴露于IL-1β显著影响了这些细胞在软骨生成和成骨条件下的分化反应，基因表达分析表明MAPK、Wnt和TLR信号通路发生了变化，同时促炎细胞因子和软骨降解酶的表达增加。这些结果突出了MSCs作为研究OA的临床前模型的价值，并为确定驱动OA病理的因素对MSCs用于新型OA治疗的治疗潜力的影响提供了依据。
