Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation.

Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli fi-galactosidase marker gene, and a third vector (Ad.RSV hL-ira) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 103 plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli j3-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface ofosteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining ofthe cartilage organ cultures forE. coli P-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-ira and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-ira-treated cartilage samples were resistant to ILl-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-i-induced extracellular matrix degradation. (J. Clin. Invest. 1995. 96:2454-2460.) Key words: arthritis * gene therapy * interleukin-1 receptor antagonist adenovirus