Characterized Chondrocyte Implantation Challenges Current Paradigms for the Treatment of Symptomatic Joint Surface Lesions

The use of autologous cells derived from an articular cartilage biopsy to treat joint surface lesions was introduced in 1994 by Brittberg and Peterson. In a 2-step procedure, chondrocytes were harvested from a minor weight-bearing area of the knee joint during arthroscopy, expanded ex vivo and implanted during an arthrotomy 2–3 weeks later. However, throughout the in vitro expansion process, articular chondrocytes progressively lose their phenotypic traits and capacity to form stable cartilage tissue, thereby jeopardizing proper in vivo repair.
Data on dedifferentiation revealed that in vivo tissue formation of stable cartilage is governed by the interaction between environmental factors and inherent phenotypical characteristics. Characterized chondrocytes are an expanded population of cartilage cells that express a marker profile predictive for the formation of ectopic hyaline-like cartilage in vivo in a consistent and reproducible manner. A controlled and consistent manufacturing process was developed to maintain this phenotype stability. This involved optimisation of the biopsy procedures and mostly the culture process parameters. Characterized viable autologous cartilage cells expanded ex vivo expressing specific marker proteins were introduced in clinical practice in 2004.
A prospective randomized multicenter controlled trial compared characterized chondrocyte implantation (CCI) to microfracture in the treatment of symptomatic cartilage defects of the femoral condyles. The primary endpoint was successfully reached at 1 year, with CCI showing superior tissue regeneration. Clinical outcome at 12–18 months measured by the overall Knee injury and Osteoarthritis Outcome Score (KOOS) was comparable for both treatments. An extension at 3 and 5 years confirmed that a good clinical outcome was maintained over time for both treatments in the overall patient population. Strikingly, sub analysis of the long-term follow-up data revealed that early treatment by CCI resulted in statistically significant and most importantly clinically relevant better results when compared to microfracture, supporting a critical window of opportunity for genuine tissue regeneration. In addition, data from a large compassionate use program, whereby lesions were treated at diverse locations in the knee joint, corroborated the benefit of CCI found in the RCT. These data sets allow now to better define the treatment algorithms for symptomatic joint surface lesions of the knee in clinical practice.