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The aim of this study was to test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress transforming growth factor-β1. A total of 163 Kellgren-Lawrence grade 3 patients with knee osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical function by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, function in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance imaging, and soluble urine and blood biomarkers. TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed toward thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although these were not statistically significant (p > 0.05). Serum C-terminal telopeptide of type I collagen (CTX-I) and urine CTX-II levels were lower over 1 year in TG-C than placebo-treated patients, with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding great potential as a disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection site pain (5%). TG-C was associated with statistically significant improvements in function and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.

Autologous chondrocyte implantation (ACI) is widely used to treat symptomatic articular cartilage injury of the knee. Fibrin ACI is a new tissue-engineering technique for the treatment of full-thickness articular cartilage defects, in which autologous chondrocytes are inserted into a three-dimensional scaffold provided by fibrin gel. The objective of this study is to document and compare mean changes in overall clinical scores at both baseline and follow-up. Fibrin ACI was used to treat deep cartilage defects of the femoral condyle in 30 patients. There were 24 men and 6 women with a median age of 35 years (range 15-55) and with a mean defect size of 5.8 cm(2) (range 2.3-12). Clinical and functional knee evaluations were performed using different scoring systems, MRI was performed 24 months postoperatively, and arthroscopy was performed 12 months postoperatively. All patients achieved clinical and functional status improvements following surgery (P < 0.01). The mean scores of the Henderson classification (MRI evaluation) significantly improved from 14.4 to 7 (P = 0.001), and no graft-associated complications were noted. Arthroscopic assessments performed 12 months postoperatively produced nearly normal (grade II) International Cartilage Repair Society scores in 8 of the 10 study patients. Fibrin ACI offers the advantages of technical simplicity, minimal invasiveness, a short surgery time, and easier access to difficult sites than classical ACI. Based on the findings of this clinical pilot study, we conclude that fibrin ACI offers a reliable means of treating articular cartilage defects of the knee.

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