Adhesion of transplanted chondrocytes onto cartilage in vitro and in vivo

Objective. The specific objectives of this study using organ culture were ( 1) to transplant chondrocytes onto an intact cartilage surface; (2) to gene tically modify endogenous and transplanted chondrocytes; and (3) to assess the ability of these cells to continually express a gene product. The speci fic objective with in vivo experiments was to transplant chondrocytes with intraarticular injections to cartilage. Methods. Fluorescent membrane and intracellular dyes were used in conjuncti on with confocal microscopy to observe the integration of transplanted chon drocytes into cartilage both in vitro and in vivo. The distribution and dur ation of binding of rat, canine, and bovine chondrocytes to cartilage expla nts and the duration of expression of genes transduced into the transplante d chondrocytes were also determined. We used the vector AdlacZ, an E1 and E 3 deleted replication defective adenoviral vector that contains the beta-ga lactosidase gene driven by the beta-actin promoter and the cytomegalovirus enhancer. Results. The transplanted chondrocytes had a patchy distribution after in v itro or in vivo transplantation and buried themselves within the cartilage over time. Chondrocytes infected with the adenoviral vector AdlacZ soon or well after transplant to cartilage explants were maintained on the cartilag e and continued throughout the duration of each trial to produce beta-galac tosidase coded by the adenoviral vector. The cartilage plugs were infected with AdlacZ at 2 days or one, 2, 5, or 8 weeks after the chondrocytes were transplanted. The cartilage slices were then cultured from 15 days for chon drocytes infected at 8 weeks to 60 days for chondrocytes infected at 2 days post-transplant before determining the expression of beta-galactosidase. Conclusion. These results support the possibility of repairing cartilage by intraarticular injections of chondrocytes. Transduction of chondrocytes wi th genes producing a variety of matrix promoting proteins should further en hance the reconstruction of osteoarthritic cartilage.