Cell and Gene Therapy for Cartilage Repair and Osteoarthritis; Genetic Enhancement of Cartilage Repair

Cartilage defects are a troublesome thing because cartilage has no regeneration capacity. The project entitled "Cell and Gene Therapy for Cartilage Repair " will be part of a research program which is already initiated to improve the repair of cartilagenous lesions at the Center for Molecular Orthopedics at Harvard Medical School in Boston. The aim of the submitted project is to show whether the implantation of chondrocytes that have been transduced with cDNA encoding TGF-ß1, IGF-1 and BMP-2 will enhance the repair of experimentally induced, full thickness lesions in the articular cartilages of rabbits. The efficiency of transduced chondrocytes for cartilage repair in vivo has not been examined in detail, yet. After transduction and implantation of chondrocytes in the submitted project it will be analyzed which of the growth factors will lead to the most effective cartilage repair defects of articular cartilage after 3 and 6 months. The following points will be estimated: 1. The survival of transduced chondrocytes in vivo. 2. The duration of the transgene expression and production of growth factors in transduced chondrocytes in vivo. 3. The quality of the regenerated cartilage by examination of the chondrocytes, matrix synthesis, and the presence of collagen type II. 4. The quality of ingrow of the transduced chondrocytes into the defect histologically. 5. If there is an effect of the locally produced growth factors to synovial cells. If the outcome of this study shows an efficient hyaline cartilage repair by using transduced chondrocytes, the project would build the base of future clinical trials. This project should provide a basis for further, future collaboration between our institutions.