Characterization of adenovirus-mediated gene transfer in rabbit flexor tendons.

PURPOSE Adenoviral vector-based gene therapy is a promising technique for the delivery of growth factors to tendons. The objective of this study was to determine whether rabbit flexor tendons could be transduced effectively by adenoviral vectors and whether the introduction of adenoviral vectors would cause a notable local inflammatory response. METHODS Recombinant adenoviruses expressing green fluorescent protein (AdGFP) or BMP-13 (AdBMP-13) were constructed and 3 different viral titers (1 x 10(7), 1 x 10(8), and 1 x 10(9)) were tested in this study. The second through fifth tendons of the forepaws and hindpaws of a New Zealand white rabbit were identified surgically and injected with different viral titers of adenoviruses. The fifth tendon was used as a control. The tendons were harvested 12 days after surgery. The retrieved tendons were sectioned to measure transgene expression, as well as for histologic evaluation. RESULTS At all tested viral titers an efficient dose-dependent transgene expression was detected in all samples at 12 days after injection. At the highest dose the injection sites were notable for lymphocytic infiltration, suggesting that injected adenoviral vectors can illicit some local inflammatory response. Lymphocytic infiltration was much less apparent, however, in the tendons injected with lower titers of adenoviral vectors. There was no evidence of a massive inflammatory response and/or cell death. CONCLUSIONS Our findings show that adenovirus-based gene therapy is an efficient means of gene delivery to rabbit flexor tendons. Transduction efficiency of transgenes was dose dependent across the tested titers, although adenovirus-induced inflammation was notable only at the highest titer. This indicates that efficient gene transfer without notable local inflammatory response may be achieved by using the lower titers. Although adenovirus-induced inflammation can be minimized by using lower viral titers, its impact on adhesion formation in the long term remains unknown.