Continuous Transforming Growth Factor β1Secretion by Cell-Mediated Gene Therapy Maintains Chondrocyte Redifferentiation

Abstract

One of the most important factors in the production of cartilage is transforming growth factor β₁ (TGF-β₁). To obtain sustained release of TGF-β₁, a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-β₁ gene. The single clone derivative showed sustained TGF-β₁ secretion. It also showed constitutive type II collagen expression. Whereas the TGF-β₁ protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-β₁ showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-β₁ as a transgene would be a promising treatment for osteoarthritis.