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Purpose of the Study: The knee has little capacity for spontaneous regeneration of deep cartilage defects. In 1999, the French Society of Arthroscopy initiated a multicentric clinical trial on autologous chondrocyte transplantation using the technique described by Brittberg and Peterson. The protocol of this prospective study was validated by the ethics committee and all patients provided the informed consent for participation., Material and Methods: Patients underwent surgery in seven hospitals: 28 patients (7 female, 21 male, mean age 28 years, age range 18-45 years). The underlying condition was: osteochondritis (n=14), isolated posttraumatic chondropathy (n=8), chondropathy plus ACL tear (n=6). All patients presented deep condylar cartilage defects (ICRS grades 3 and 4). Mean surface area involved after debridement was 490 mm2 (range 150-1050 mm2). Patients were reviewed two years at least after transplantation for functional assessment and an MRI performed 2 to 3 years after transplantation. Control arthroscopy was also performed in 13 patients with biopsy for histology and immunohistochemistry for 10., Results: Twenty-six patients were reviewed with more than two years follow-up (mean 2 years 9 months). There were no general complications; three patients presented a partial avulsion of the autograft treated arthroscopically and one arthrolysis was performed at six months. Function was improved in all patients but four, but pain persisted in one patient. The mean ICRS score improved from 41 points (19-55 points) to 74 points (54-86 points), for an 80% gain. Follow-up MRI was available for 16 knees: the graft was hypertrophied in 11, at level in 3 and insufficient in 2; marginal integration was good in 10 knees and fair in 6. Items of marginal and subchondral integration had a very high positive predictive value for good clinical outcome. The arthroscopic score was nearly normal (range 8-11) in 8 knees and abnormal (range 4-7) in 5. The Knutsen histological groups according to richness of hyaline cartilage were: group 1 (>60%) (n=1); group 2 (>40%) (n=3), group 3 (<40%) n(=4) and group 4 (bone or fibrous tissue) (n=1). The function scores (r=0.80) and the MRI scores (r=0.76) were correlated with the arthroscopy scores. There was no correlation between the histological findings but the sample size was too small for meaningful analysis., Discussion: The clinical results demonstrate an improvement in more than 80% of knees, findings similar to earlier reports. The arthroscopic and histological results were equivalent to those reported by Knutsen, but less satisfactory than those reported by Bentley or Peterson. Cell injections under a periosteal patch constitute the first generation of autologous chondrocyte grafts. Resorbable matrices loaded with chondrocytes before implantation are under development and have provided promising early results.

APOPTOSIS IN JOINT CARTILAGE: Apoptosis is the physiologically programmed death of cells to be distinguished from necrosis which caused non-programmed cell death. In joint cartilage, more than 50% of the chondrocytes show signs of apoptosis compared with 10% in normal cartilage. ROLE OF NITRIC OXIDE: In osteoarthritis the production of nitric oxide (NO) appears to be increased, inducing apoptosis of articular chondrocytes stimulated by interleukin 1. NO inhibitors can limit the progression of experimentally induced joint lesions in animal models. IN VITRO RESULTS: The protective effect of the chondroitin sulfates CS4 and CS6 against death of chondrocytes exposed to NO has been demonstrated in vitro. Chondrocytes for New Zealand white rabbits were cultivated in the presence of an NO donor for exposure durations from 12 to 72 hours, with or without adding CS 4&6 to the culture medium. After 3 days of culture, NO induced a significant rise in the number of apoptotic chondrocytes. In 70% of the cases, preventive treatment with 100 micrograms/ml CS 4&6 lowered the number of dead cells. This cytoprotective effect reached a mean 28% and was inversely dependent on the duration of exposure to the NO donor.