Virusvermittelter Gentransfer in die Patellarsehne. Eine experimentelle Studie am Kaninchen

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 that encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study, different viral vectors and liposomes are evaluated for their ability to deliver genes to cells of ligamentous and meniscal origin. The ACL, PCL, MCL, semitendinosus tendon, patellar tendon, and menisci were harvested from New Zealand white rabbits. Cells grown from these tissues were then investigated 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 shortterm experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells could be increased by the use of the selectable marker gene neo(r). Cells infected with adeno-associated virus containing the neo(r)-gene could also be 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 could be observed preferentially in the subsynovial layer at a declining frequency over a 6-week period. The allogeneous 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.