Allogenic Bioengineered Cartilage Achieves Hyaline Cartilage Repair in a Large Animal Model: A Promising Step Forward

Halah Kutaish, Laura Bengtsson, Sana Boudabbous, François Lazeyras, Sebastien Courvoisier, Vincent Braunersreuther, Sabine E. Hammer, Didier Hannouche, Jacques Ménétrey, Vannary Tieng, Philippe M. Tscholl
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Abstract

Background: Chondrocyte-based cell therapy remains a promising method for cartilage repair, despite limitations faced during the last 30 years. Purpose/Hypothesis: This work presents hyaline-like bioengineered beads from donor chondrocytes as a novel treatment option for cartilage lesions. It was hypothesized that the implanted cartilage minigrafts would be able to treat cartilage lesions by complete fusion among themselves and by integration with surrounding tissue. No tissue rejection was expected because of cartilage’s reported immunological privilege. Study Design: Controlled laboratory study. Methods: Allogenic cartilage beads with hyaline characteristics were produced from frozen chondrocytes of a minipig donor. A total of 8 Göttingen minipigs underwent the implantation of bioengineered cartilage beads into 8 to 10 mm–diameter full-thickness chondral lesions (3 lesions/knee). Animals were sacrificed at 6 weeks (n = 2) and 6 months (n = 6) after implantation. The safety and efficacy of implantation were assessed by macroscopic and histological analyses as well as by magnetic resonance imaging. Results: No signs of acute or chronic rejection were observed in any study animals upon implantation. For 6 minipigs at 6 months, magnetic resonance imaging results showed better coverage of the grafted lesions compared with empty (control) lesions. When the cartilage beads were maintained in the lesion, complete integration of the minigrafts with surrounding subchondral bone and native cartilage was observed. Repair tissue in grafted lesions maintained hyaline-like quality and showed evidence of a chondral zonal arrangement at 6 months’ follow-up. Additionally, grafted lesions (n = 17) had better macroscopic repair scores than empty lesions (n = 7) (mean inverse Goebel score, 4.24 and 5.57, respectively). Graft-filled lesions showed only a slight superiority in histological repair scores (mean Bern score, 5.76 and 5.43, respectively). Conclusion: Allogenic cartilage beads hold potential as an advanced therapy medicinal product for treating cartilage lesions in 1-step surgery with established safety and efficacy. Clinical Relevance: This successful preclinical study highlights allogenic cartilage beads as a promising method for cartilage repair. Moreover, using donor chondrocytes may allow reduced patient morbidity and 1-step surgery. Hence, this advanced therapy medicinal product is suitable for treating large lesions and older patients and is currently being evaluated in a phase I/IIa clinical trial.
同种异体生物工程软骨在大型动物模型中实现透明软骨修复:有希望的一步
背景:基于软骨细胞的细胞疗法仍然是一种很有前途的软骨修复方法,尽管在过去的30年里面临着局限性。目的/假设:这项工作提出了来自供体软骨细胞的透明样生物工程珠作为软骨病变的一种新的治疗选择。据推测,植入的微型软骨能够通过软骨之间的完全融合和与周围组织的融合来治疗软骨病变。没有组织排斥预期,因为软骨的免疫特权报道。研究设计:实验室对照研究。方法:利用小型猪供体的冷冻软骨细胞制备具有透明特征的同种异体软骨珠。8只Göttingen迷你猪在直径为8 ~ 10 mm的全层软骨病变(3个/膝)内植入生物工程软骨珠。动物分别于植入后6周(n = 2)和6个月(n = 6)处死。通过宏观、组织学分析和磁共振成像评价植入的安全性和有效性。结果:在任何研究动物中,没有观察到急性或慢性排斥反应的迹象。对于6只6个月大的小型猪,磁共振成像结果显示,与空白(对照)病变相比,移植病变的覆盖率更高。当软骨珠维持在病变部位时,观察到微型人工骨与周围软骨下骨和天然软骨完全融合。在6个月的随访中,移植病变的修复组织保持透明样质量,显示软骨带状排列的证据。此外,移植病变(n = 17)的宏观修复评分优于空病变(n = 7)(平均逆格贝尔评分分别为4.24和5.57)。移植物填充病变在组织学修复评分上仅表现出轻微的优势(平均Bern评分分别为5.76和5.43)。结论:同种异体软骨珠有潜力作为一种先进的治疗药物,在一步手术中治疗软骨病变,安全性和有效性已得到证实。临床意义:这项成功的临床前研究突出了同种异体软骨珠作为软骨修复的一种有前途的方法。此外,使用供体软骨细胞可以降低患者的发病率和一步手术。因此,这种先进的治疗药物适用于治疗大病变和老年患者,目前正在I/IIa期临床试验中进行评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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