CO.DON AG, 14513 Teltow, Germany.
Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
Int J Mol Sci. 2021 Jul 1;22(13):7149. doi: 10.3390/ijms22137149.
Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.
自体软骨细胞移植（ACI）是一种治疗局灶性软骨缺损的细胞疗法。目前在欧盟（EU）批准使用的 ACI 产品由自体基质相关软骨细胞的球体组成。这些球体是体外扩增的人类自体软骨细胞及其自身合成的细胞外基质的球形聚集物。本研究旨在概述已进行的临床前和非临床研究，以确保细胞疗法具有可重复的质量、安全性和疗效，并评估基于球体的 ACI 的临床数据。进行了系统评价，以纳入所有关于在自体血清中培养的自体聚集软骨细胞球体的英文出版物，不包括其他补充剂。共纳入 20 篇出版物，其中 7 篇为临床前和非临床研究出版物，13 篇为临床研究出版物。临床前和非临床研究出版物描述了从概念发展到体内功效以及与质量和安全性相关的方面，如生物分布、致瘤性、遗传稳定性和效力。临床研究的评估表明，基于球体的 ACI 治疗软骨缺损在随机临床试验中具有短期至中期的安全性和疗效，这些临床试验选择了特定患者，并且在为更复杂的患者提供真实世界数据的常规治疗中也具有疗效。
