Gene transfer to adult human lung tissue ex vivo

The potential of gene therapy for treatment of lung disease remains unreali sed. Early model systems often resulted in promising efficiency of gene tra nsfer only to prove irreproducible in the clinic. While problems such as in duction of host immune responses and duration of expression also need to be addressed, it is now widely believed that alternative, relevant models whi ch more accurately reflect gene transfer efficiencies in human lungs are ur gently required. We report here on a human lung slice culture system to ass ess gene transfer to adult lung epithelium. A lacZ-expressing adenovirus (A dCA35lacZ) was used as a reporter vector. A solution of AdCA35lacZ was inst illed via bronchioles into resected lung tissue, a route analogous to clini cal administration. Following a 1 h incubation, the tissue was inflated wit h a 0.4% agarose solution, instilled via the same bronchioles. Once solidif ied, 500 mu m slices of the tissue were prepared and cultured for 4 days. b eta-Galactosidase staining revealed lacZ transgene expression in bronchiola r and alveolar cells: of the lung slices throughout the 4 days in culture. This system, which can also be used to study other viral and liposome vecto rs, could prove to be a useful alternative model for assessing gene deliver y to adult human lung epithelium.