TY - JOUR
T1 - Role of matrix‐associated autologous chondrocyte implantation with spheroids in the treatment of large chondral defects in the knee
T2 - A systematic review
AU - Vonk, Lucienne Angela
AU - Roël, Giulietta
AU - Hernigou, Jacques
AU - Kaps, Christian
AU - Hernigou, Philippe
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
KW - Advanced therapy medicinal product
KW - Autologous chondrocyte implantation
KW - Cartilage defects
KW - Preclinical research
KW - Spheroids
KW - Spherox
UR - http://www.scopus.com/inward/record.url?scp=85108980307&partnerID=8YFLogxK
U2 - 10.3390/ijms22137149
DO - 10.3390/ijms22137149
M3 - Review article
C2 - 34281202
AN - SCOPUS:85108980307
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 13
M1 - 7149
ER -