Current cartilage regenerative therapies are not fully effective in treating osteoarthritis of the knee (OAK). We have developed chondrocyte sheets for autologous transplantation and tested these in in vitro and in vivo preclinical studies, and have reported that the transplantation of chondrocyte sheets promoted hyaline cartilage repair in rat, rabbit, and minipig models. However, autologous transplantation of chondrocyte sheets has yet to be reported in humans. Here, we report our combination therapy in which conventional surgical treatment for OAK, is followed by autologous chondrocyte sheet transplantation for cartilage repair. Eight patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV receive the therapy. Patients are thoroughly assessed by preoperative and postoperative X-rays, magnetic resonance imaging (MRI), arthroscopy, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score (LKS), and a laser-induced photoacoustic method to assess cartilage viscoelasticity. Arthroscopic biopsies of all patients are performed 12 months after transplantation for histological evaluation. The properties of the chondrocyte sheets are evaluated using gene expression analysis to investigate the ability to predict the clinical and structural outcomes of the therapy. For this small initial longitudinal series, combination therapy is effective, as assessed by MRI, arthroscopy, viscoelasticity, histology, and the clinical outcomes of KOOS and LKS. Gene marker sets identified in autologous chondrocyte sheets may be predictive of the overall KOOS, LKS, and histological scores after therapy. These predictive gene sets may be potential alternative markers for evaluating OAK treatment.

目前的软骨再生疗法对于治疗膝骨关节炎（OAK）并不完全有效。我们开发了用于自体移植的软骨细胞片，并在体外和体内临床前研究中对其进行了测试，并报道了软骨细胞片的移植促进了大鼠、兔子和小型猪模型中的透明软骨修复。然而，软骨细胞片自体移植在人类中尚未有报道。在这里，我们报告我们的联合疗法，其中对 OAK 进行常规手术治疗，然后进行自体软骨细胞片移植以进行软骨修复。八名患有 OAK 和软骨缺陷（经关节镜分类为 Outerbridge III 级或 IV 级）的患者接受了治疗。通过术前和术后 X 射线、磁共振成像 (MRI)、关节镜检查、膝关节损伤和骨关节炎结果评分 (KOOS)、Lysholm 膝关节评分 (LKS) 以及激光诱导光声方法来评估软骨粘弹性，对患者进行全面评估。移植后12个月对所有患者进行关节镜活检以进行组织学评估。使用基因表达分析评估软骨细胞片的特性，以研究预测治疗的临床和结构结果的能力。对于这个小型的初始纵向系列，根据 MRI、关节镜检查、粘弹性、组织学以及 KOOS 和 LKS 的临床结果评估，联合治疗是有效的。自体软骨细胞片中鉴定的基因标记集可以预测治疗后的总体 KOOS、LKS 和组织学评分。这些预测基因集可能是评估 OAK 治疗的潜在替代标记。