Background:Osteoarthritis (OA) is a prevalent and disabling disease that affects a significant proportion of the global population. Urine-derived stem cells (USCs) have shown great prospects in the treatment of OA, but there is no study that has compared them with traditional stem cells.Purpose:This study aimed to compare the therapeutic efficacy and mechanisms of USCs and adipose-derived stem cells (ADSCs) for OA treatment.Study Design:Controlled laboratory study.Methods:We compared the biological properties of USCs and ADSCs using CCK-8, colony formation, EdU, adhesion, and apoptosis assays. We evaluated the protective effects of USCs and ADSCs on IL-1β–treated OA chondrocytes by chemical staining, immunofluorescence, and Western blotting. We assessed the effects of USCs and ADSCs on chondrocyte autophagy by transmission electron microscopy, immunofluorescence, and Western blotting. We also compared the therapeutic efficacy of intra-articular injections of USCs and ADSCs by gross, histological, micro–computed tomography, and immunohistochemical analyses in an OA rat model induced by anterior cruciate ligament transection.Results:USCs showed higher proliferation, colony formation, DNA synthesis, adhesion, and anti-apoptotic abilities than ADSCs. Both USCs and ADSCs increased the expression of cartilage-specific proteins and decreased the expression of matrix degradation–related proteins and inflammatory factors in OA chondrocytes. USCs had a greater advantage in suppressing MMP-13 and inflammatory factors than ADSCs. Both USCs and ADSCs enhanced autophagy in OA chondrocytes, with USCs being more effective than ADSCs. The autophagy inhibitor 3-MA reduced the enhanced autophagy and protective effects of USCs and ADSCs on OA chondrocytes.Conclusion:To our knowledge, this is the first study to explore the efficacy of USCs in the treatment of knee OA and to compare them with ADSCs. Considering the superior properties of USCs in terms of noninvasive acquisition, a high cost-benefit ratio, and low ethical concerns, our study suggests that they may be a more promising therapeutic option than ADSCs for OA treatment under rigorous regulatory pathways.Clinical Relevance:USCs may be a superior cell source for stem cells to treat knee OA, and this study strengthens the evidence for the application of USCs.

中文翻译：

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尿源干细胞和脂肪源干细胞在骨关节炎中的治疗效果和自噬介导的作用机制的比较


背景： 骨关节炎 （OA） 是一种普遍的致残性疾病，影响全球人口的很大一部分。尿液来源干细胞 （USC） 在治疗 OA 方面显示出巨大的前景，但没有研究将它们与传统干细胞进行比较。目的： 本研究旨在比较 USCs 和脂肪来源干细胞 （ADSC） 治疗 OA 的疗效和机制。研究设计： 对照实验室研究。方法： 我们使用 CCK-8 、菌落形成、 EdU 、粘附和细胞凋亡测定比较 USCs 和 ADSCs 的生物学特性。我们通过化学染色、免疫荧光和 Western blotting 评估了 USCs 和 ADSCs 对 IL-1β 处理的 OA 软骨细胞的保护作用。我们通过透射电子显微镜、免疫荧光和 Western blotting 评估了 USCs 和 ADSCs 对软骨细胞自噬的影响。我们还通过肉眼、组织学、显微计算机断层扫描和免疫组织化学分析在前交叉韧带横断诱导的 OA 大鼠模型中比较了关节内注射 USCs 和 ADSC 的治疗效果。结果： USCs 表现出比 ADSCs 更高的增殖、集落形成、 DNA 合成、粘附和抗凋亡能力。USCs 和 ADSCs 均增加 OA 软骨细胞中软骨特异性蛋白的表达，并降低基质降解相关蛋白和炎症因子的表达。USCs 在抑制 MMP-13 和炎症因子方面比 ADSC 具有更大的优势。USCs 和 ADSCs 都增强了 OA 软骨细胞的自噬，其中 USCs 比 ADSC 更有效。自噬抑制剂 3-MA 降低了 USCs 和 ADSCs 对 OA 软骨细胞的增强自噬和保护作用。结论： 据我们所知，这是第一项探讨 USCs 治疗膝关节 OA 的疗效并将其与 ADSCs 进行比较的研究。考虑到 USC 在无创获取、高成本效益比和低伦理问题方面的优越特性，我们的研究表明，在严格的监管途径下，它们可能是比 ADSCs 更有前途的 OA 治疗选择。临床相关性： USCs 可能是干细胞治疗膝关节 OA 的优质细胞来源，本研究加强了 USCs 应用的证据。