674. Molecular, Biochemical and Biomechanical Analysis of Articular Cartilage Repaired with Genetically Modified Chondrocytes Expressing Insulin-Like Growth Factor-I

Insulin-like growth factor-I (IGF-I) has been shown to be important for normal articular chondrocyte function. Gene therapy offers the prospect of extending the time IGF-I is released in cartilage injury. The purpose of this study was to investigate the molecular, biochemical and biomechanical effects of AdIGF-I genetically modified chondrocytes on the repair and surrounding tissue compared to defects implanted with naïve chondrocytes.Sixteen horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint was repaired with AdIGF-I transduced chondrocytes (20×10 6 ) and the opposite was implanted with the same number of control (uninfected) chondrocytes. Horses were sacrificed 4 weeks, 9 weeks, and 8 months. At necropsy, the gross appearance of repair tissue was evaluated. Repair tissue was removed for RNA and DNA. Histological, immunohistochemical, in situ hybridization, biochemical analysis for collagen Type II and proteoglycan content were performed. Taqman PCR was performed to measure mRNA content of repair tissue to compare IGF-I and collagen type II. Biomechanical analysis was also performed.Gross and histological scores were improved for the genetically modified repair tissue at 4 and 9 weeks and 8 months. Type II collagen content was also increased in the AdIGF-treated group and in immunohistochemical analysis as well as by biochemical analysis. Taqman PCR analysis revealed IGF-I and Collagen Type II expression in the AdIGF-treated group was elevated over control (p