epartment of Orthopaedics and Otorhinolaryngology, Erasmus MC, University Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, the
Eur Cell Mater. 2018 Nov 6;36:218-230. doi: 10.22203/eCM.v036a16.
Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug.
间充质干细胞（MSCs）作为一种治疗骨关节炎（OA）的方法，具有很大的治疗潜力。MSCs 分泌的因子可以对抗炎症和分解代谢过程，并吸引内源性修复细胞。在胶原酶诱导的 OA 小鼠模型中，研究了关节内注射 MSC 分泌组对 OA 相关疼痛、软骨损伤、软骨下骨改变和滑膜炎的影响。MSC 分泌组通过用干扰素 γ（IFNγ）和肿瘤坏死因子 α（TNFα）刺激人骨髓来源的 MSC 产生。54 只小鼠被随机分配接受以下注射：i）来自 20000 个 MSC 的 MSC 分泌组，ii）20000 个 MSC 或 iii）培养基（对照）。通过后肢重量分布评估疼痛。通过组织学评估软骨损伤、软骨下骨体积和滑膜炎。与对照组相比，MSC 分泌组和 MSC 注射组在第 7 天时疼痛减轻。与健康膝关节相比，对照组的软骨损伤更为严重，但在 MSC 分泌组或 MSC 治疗的膝关节中未发现这种差异。滑膜炎、软骨下骨体积或不同巨噬细胞亚型的存在均未观察到影响。与注射 MSCs 类似，注射 MSC 分泌组可早期减轻疼痛，并可防止在小鼠 OA 模型中软骨损伤的发展。通过利用 MSC 分泌因子的再生能力，可以极大地提高该方法的标准化、可负担性和临床转化能力。这样，这种生物疗法可以发展成为一种真正的治疗骨关节炎的药物。
