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) t o chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies inc luding osteoarthritis. In this study, gene delivery to human osteoarth ritis chondrocytes in monolayer culture was demonstrated using two ade noviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1 ra) containing the cDNA for human interleukin-1 receptor antagonist. A t an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infec ted cells stained positive for E. coli beta-galactosidase activity, in dicating a high efficiency of transduction. Genetically modified chond rocytes were then transplanted onto the articular surface of osteoarth ritic cartilage organ cultures with and without the underlying subchon dral bone. Both in situ staining of the cartilage organ cultures for E . coli beta-galactosidase activity and examination by scanning electro n microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transge nic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded on to the surface of osteoarthritic cartilage secreted high levels of bio logically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradati on over 10 d of sustained organ culture. These data demonstrate that t ransplantation of transduced chondrocytes onto the articular surface p rotects cartilage from IL-1-induced extracellular matrix degradation.