Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany.
Gelenkzentrum Rhein-Main, 65239 Hochheim, Germany.
Cells. 2024 Mar 20;13(6):546. doi: 10.3390/cells13060546.
The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.
目前治疗大软骨缺损的金标准是自体软骨细胞移植（ACT）。作为一种新的软骨再生手术方法，切碎软骨植入（MCI）越来越受到关注。本研究旨在探讨在 TNFα 等促炎细胞因子的标准化炎症模型中，与分离培养的软骨细胞相比，软骨碎片的软骨生成情况。根据 ACT 方法，从牛软骨中分离培养软骨细胞至第 3 代，并进行球体培养。同时，将软骨碎片（<1mm）制成软骨碎片。添加 TNFα（20ng/ml）模拟炎症过程。与未传代的软骨细胞相比，TNFα 对传代软骨细胞的影响更强，对分离软骨细胞和软骨碎片的基因表达谱有不同的影响。MCI 对 TNFα 的敏感性较低，IL-6 释放减少，对炎症标志物的影响较小。生化和组织学分析支持了这些发现，表明与未传代细胞和 MCI 构建体相比，TNFα 对传代微球培养物的负面影响更大。本研究表明 TNFα 在软骨细胞球体培养和软骨碎片模型中对软骨生成有负面影响。与未传代细胞相比，传代软骨细胞对细胞因子的影响更为敏感。这表明，与 ACT 相比，MCI 可能在骨关节炎条件下具有更好的再生潜力。需要进一步的研究将这些发现转化为临床实践。
