TRANSPLANTATION OF ADENOVIRALLY TRANSDUCED ALLOGENEIC CHONDROCYTES INTO ARTICULAR-CARTILAGE DEFECTS IN-VIVO

Gene transfer to chondrocytes followed by intra-articular transplantat ion may allow for functional modulation of chondrocyte biology and enh anced repair of damaged articular cartilage. We chose to examine the l oss of chondrocytes transduced with a recombinant adenovirus containin g the gene for Escherichia. coli beta-galactosidase (Ad.RSVntlacZ), fo llowed by transplantation into deep and shallow articular cartilage de fects using New Zealand White rabbits as an animal model. A type I col lagen matrix was used as a carrier for the growth of the transduced ch ondrocytes and to retain the cells within the surgically created artic ular defects. Histochemical analysis of matrices recovered from the an imals 1, 3 and 10 days after implantation showed the continued loss of lacZ positive chondrocytes. The number of cells recovered from the ma trices was also compared with the initial innoculum of transduced cell s present within the matrices at the time of implantation. The greates t loss of transduced cells was observed in the first 24 h after implan tation. The numbers of transduced cells present within the matrices we re relatively constant between I and 3 days postimplantation, but had progressively declined by 10 days postimplantation. These results sugg est that transduction of chondrocytes followed by intra-articular tran splantation in this rabbit model may enable us to examine the biologic al effects of focal transgenic overexpression of proteins involved in cartilage homeostasis and repair.