E. Messina et al., SURFACTANT PROTEIN A-PRODUCING CELLS IN HUMAN FETAL LUNG ARE GOOD TARGETS FOR RECOMBINANT ADENOVIRUS-MEDIATED GENE-TRANSFER, Pediatric research, 40(1), 1996, pp. 142-147
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
.