Surfactant protein A-producing cells in human fetal lung are good targets for recombinant adenovirus-mediated gene transfer

Local delivery of Escherichia coli β-galactosidase gene (β-gal) to surfactant protein-A (SP-A)-producing cells by a replication-defective recombinant adenovirus (AdCMV.β-gal) was tested in human 8-12-wk-old fetal lung explants cultured in Waymouth's medium. In contrast to uninfected explants, direct addition of 0.8-1.6 x 10⁶ plaque-forming units of AdCMV.β- gal resulted in β-galactosidase (β-Gal)-specific staining of the pulmonary epithelium. SP-A localization by indirect immunofluorescence showed positive specific staining of the β-Gal¹ lung epithelial cells, demonstrating that recombinant-defective adenoviruses efficiently gene expression in SPA⁺ cells persisted for more than 1 mo. No apparent alteration of morphology, phenotype, and growth was observed. The in vitro human lung model described may be useful for testing DNA constructs for vector-mediated gene therapy, as an approach to the treatment of congenital defects and neonatal disorders, such as respiratory distress syndrome and bronchopulmonary dysplasia.