Alveolar stem cell transduction by an adeno-associated viral vector.
In inherited disorders such as surfactant protein deficiencies or cystic fibrosis (CF), where lung damage develops progressively after birth, gene replacement is best accomplished in the neonatal period. We use the adeno-associated virus (AAV) as a vector for gene transfer in the newborn rabbit lung where stem cells are activated for lung growth and differentiation. AAV-mediated gene transfer as assayed by lacZ gene expression occurred preferentially in alveoli in the alveolar epithelial progenitor cell, the type II cell, and in the large airway tracheobronchial basal and ciliated cells. Cell proliferation was confirmed by 5-bromo-deoxyuridine (BRDU) labeling in regions undergoing alveolarization and airway branch points. Regions of cell proliferation coincided with areas of significant lacZ expression. Thus, dividing and differentiating cells can be targeted by AAVlacZ delivery to newborn lung.
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
P L
PL
Zeitlin
S
S
Chu
C
C
Conrad
U
U
McVeigh
K
K
Ferguson
T R
TR
Flotte
W B
WB
Guggino
D000818:Animals; D000831:Animals, Newborn; D001980:Bronchi / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D007633:Keratins / Q000032:analysis; D007958:Leukocyte Count; D011510:Proteolipids / Q000032:analysis; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis; D011817:Rabbits; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology; D014132:Trachea / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D007633:Keratins; D004247:DNA; D001616:beta-Galactosidase