Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode. Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients. The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events. In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.

中文翻译：

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Nanofat 对骨关节炎的疼痛缓解和软骨修复：临床前和临床证据

骨关节炎 (OA) 是最常见的关节退行性疾病，迄今为止几乎没有有效的治疗方法。Nanofat 是一种从脂肪组织中提取的细胞混合物，具有再生能力并具有治疗 OA 的潜力。本研究旨在从基础和临床两个方面确定纳米脂肪的抗OA功效并探讨其作用模式。进行流式细胞术以表征纳米脂肪。使用单碘乙酸盐诱导的 OA 大鼠模型进行体内研究。进行细胞活力和伤口愈合测定用于体外研究。应用实时荧光定量 PCR 和蛋白质印迹分析来探索 Nanofat 的分子作用模式。此外，还进行了回顾性分析以确定 Nanofat 对膝关节 OA 患者的临床疗效和安全性。体内实验结果表明，Nanofat 显着减轻疼痛症状并保护软骨 ECM（Col2）免受损伤，其作用与脂肪组织来源的干细胞无显着差异（均 P > 0.05）。体外结果表明，Nanofat促进软骨细胞的细胞活力和迁移，显着恢复IL-1β诱导的Col2、Aggrecan、Sox9、Adamts5、Mmp3、Mmp9、Mmp13、IL-6和Col10的异常基因表达和蛋白表达。软骨细胞的 Col2、MMP9、MMP13 和 Sox9。Nanofat 对软骨细胞的这些合成代谢、分解代谢和肥大分子的调节作用在两种处理途径之间是相似的：共培养和条件培养基，表明 Nanofat 是基于旁分泌的作用模式。而且，临床数据显示，纳米脂肪可减轻OA患者的疼痛并修复受损的软骨，无不良反应。总之，本研究证明了 Nanofat 的抗 OA 功效以及基于旁分泌的作用模式，提供了 Nanofat 的新知识，并表明它是一种有前景且实用的 OA 临床治疗细胞疗法。