Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal tracheal xenografts in SCID mice.
We measured, the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. In non-CF xenografts, sequential addition of amiloride, forskolin, and ATP resulted in a 39.4% decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and +68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.
Tirouvanziam
R
R
Institut d'Embryologie Cellulaire et Moléculaire du Centre National de la Recherche Scientifique-Unité Propre de Recherche 9064, Nogent sur Marne, France.
Desternes
M
M
Saari
A
A
Puchelle
E
E
Péault
B
B
Chinet
T
T
D000818:Animals; D000013:Congenital Abnormalities / Q000196:embryology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000196:embryology* / Q000503:physiopathology*; D004594:Electrophysiology; D016332:Fetal Tissue Transplantation; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D014132:Trachea / Q000196:embryology* / Q000503:physiopathology*; D014183:Transplantation, Heterologous