Chondrocyte Implantation for Treatment of Articular Cartilage

A. Khodiev
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Abstract

Background: Because articular chondrocyte-based Autologous Chondrocyte Implantations (ACIs) have restrictively restored articular cartilage defects, alternative cell sources as a new therapeutic option for cartilage repair have been introduced. Purpose: To assess whether implantation of a Costal Chondrocyte–Derived Pellet-Type (CCP) ACI allows safe, functional, and structural restoration of full-thickness cartilage defects in the knee. Study Design Case series: Level of evidence, Methods: In this first-in-human study, 7 patients with symptomatic, full-thickness cartilage lesions were enrolled. The chondrocytes isolated from the patients’ costal cartilage were expanded, followed by 3-dimensional pellet culture to prepare the CCP-ACI. Implantation of the pellets was performed via minimal arthrotomy and secured with a fibrin sealant. Clinical scores, including the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scores, were estimated preoperatively and at 1, 2, and 5 years postoperatively. High-resolution magnetic resonance imaging was also performed to evaluate cartilage repair as well as to calculate the MOCART (magnetic resonance observation of cartilage repair tissue) score. Results: The costal chondrocytes of all patients formed homogeneous-sized pellets, which showed the characteristics of the hyaline cartilaginous tissue with lacunae-occupied chondrocytes surrounded by glycosaminoglycan and type II collagen-rich extracellular matrix. There were no treatment-related serious adverse events during the 5-year follow-up period. Significant improvements were seen in all clinical scores from preoperative baseline to the 5-year follow-up (IKDC subjective score, 34.67 to 75.86; Lysholm score, 34.00 to 85.33; Tegner activity score, 1.17 to 4.67; and MOCART score, 28.33 to 83.33). Two patients had complete defect filling on magnetic resonance imaging evaluation at 1 year. Moreover, at 5 years postoperatively, complete defect filling was observed in 4 patients, and hypertrophy or incomplete defect filling (50%-100%) was observed in 2 patients. Conclusion: The overall results of this clinical study suggest that CCP-ACI can emerge as a promising therapeutic option for articular cartilage repair with good clinical outcomes and structural regeneration and with stable results at midterm follow-up.
软骨细胞植入治疗关节软骨
背景:由于基于关节软骨细胞的自体软骨细胞植入(ACIs)有限制地修复了关节软骨缺损,替代细胞来源作为软骨修复的一种新的治疗选择已经被引入。目的:评估肋软骨细胞衍生颗粒型(CCP) ACI植入是否能安全、功能和结构地修复膝关节全层软骨缺损。研究设计病例系列:证据水平,方法:在这项首次人体研究中,纳入了7例有症状的全层软骨病变患者。从患者肋软骨中分离软骨细胞进行扩增,然后进行三维微球培养制备CCP-ACI。通过最小关节切开术植入微球,并用纤维蛋白密封剂固定。临床评分,包括国际膝关节文献委员会(IKDC)主观评分、Lysholm评分和Tegner活动评分,在术前和术后1年、2年和5年进行评估。同时进行高分辨率磁共振成像评估软骨修复情况,并计算软骨修复组织磁共振观察(MOCART)评分。结果:所有患者肋软骨细胞均形成大小均匀的微球,表现为透明软骨组织的特征,软骨细胞被陷窝占据,被糖胺聚糖和富含II型胶原的细胞外基质包围。5年随访期间未发生与治疗相关的严重不良事件。从术前基线到5年随访,所有临床评分均有显著改善(IKDC主观评分,34.67 ~ 75.86;Lysholm评分34.00 ~ 85.33;Tegner活动评分,1.17 ~ 4.67;MOCART评分28.33 ~ 83.33)。2例患者1年时磁共振成像评价缺损完全填充。术后5年4例缺损完全填充,2例缺损肥大或不完全填充(50% ~ 100%)。结论:本临床研究的总体结果表明,CCP-ACI可作为关节软骨修复的一种有前景的治疗选择,具有良好的临床效果和结构再生,中期随访结果稳定。
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