Continuous transforming growth factor β1 secretion by cell-mediated gene therapy maintains chondrocyte redifferentiation

One of the most important factors in the production of cartilage is transforming growth factor beta(1) (TGF-beta(1)). To obtain sustained release of TGF-beta(1), a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-beta(1) gene. The single clone derivative showed sustained TGF-beta(1) secretion. It also showed constitutive type II collagen expression. Whereas the TGF-beta(1) protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-beta(1) showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-beta(1) as a transgene would be a promising treatment for osteoarthritis.