Gene transfer to the patellar tendon - An experimental study in rabbits

Growth factors have the potential to enhance native repair responses in ligamentous and meniscal lesions. However, methods for applying these cytokines to sites of injury for extended periods are lacking. We suggest that local transfer of genes which encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study different viral vectors and liposomes were evaluated for their ability to deliver genes to cells of ligamentous and meniscal origin. The anterior (ACL) and posterior (PCL) cruciate ligaments and the medial collateral ligament (MCL), semitendinosus tendon, patellar tendon, and menisci were removed from New Zealand white rabbits. Cells grown from these tissues were then investigat ed for their susceptibility to genetic alteration by these vectors. Based upon the ability of these vectors to convert cells in culture to a lacZ(+) phenotype, adenovirus was the most effective vector in short-term experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells was increased by the use of the selectable marker gene neo(r). Cells infected with adeno-associated virus containing the neo(r)-gene were also selected in this way. Liposomes showed low efficiency of gene transfer and expression. In an in vivo marker study we injected adenovirus into the rabbit patellar tendon. Transduced cells were observed mainly in the subsynovial layer at a declining frequency over a 6-week period. The allogeneic transplantation of retrovirally-transduced fibroblasts into the patellar tendon resulted in a greater number of transduced cells. Although the number of lacZ(+) cells declined with time, positive cells were still present 6 weeks after transplantation. Furthermore, the transplanted cells, unlike cells transduced in situ with adenovirus, migrated from the injection site and integrated into the crimp of the tendon.