SURFACTANT PROTEIN A-PRODUCING CELLS IN HUMAN FETAL LUNG ARE GOOD TARGETS FOR RECOMBINANT ADENOVIRUS-MEDIATED GENE-TRANSFER

Local delivery of Escherichia coil beta-galactosidase gene (beta-gal) to surfactant protein-A (SP-A)-producing cells by a replication-defect ive recombinant adenovirus (AdCMV.beta-gal) was tested in human 8-12-w k-old fetal lung explants cultured in Waymouth's medium. In contrast t o uninfected explants, direct addition of 0.8-1.6 x 10(6) plaque-formi ng units of AdCMV.beta-gal resulted in beta-galactosidase (beta-Gal)-s pecific staining of the pulmonary epithelium. SP-A localization by ind irect immunofluorescence showed positive specific staining of the beta -Gal(+) lung epithelial cells, demonstrating that recombinant-defectiv e adenoviruses efficiently transfer reporter genes to fetal lung SP-A( +) cells. The reporter gene expression in SPA(+) cells persisted for m ore than 1 mo. No apparent alteration of morphology, phenotype, and gr owth was observed. The in vitro human lung model described may be usef ul 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 .