title: Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator.
abstract: Cystic fibrosis, an autosomal recessive disorder caused by a mutation in a gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), remains a leading cause of childhood respiratory morbidity and mortality. The respiratory consequences of cystic fibrosis include the generation of thick, tenacious mucus that impairs lung clearance, predisposing the individual to repeated and persistent infections, progressive lung damage and shortened lifespan. Currently there is no cure for cystic fibrosis. With this in mind, we investigated the ability of human amnion epithelial cells (hAECs) to express functional CFTR. We found that hAECs formed 3-dimensional structures and expressed the CFTR gene and protein after culture in Small Airway Growth Medium (SAGM). We also observed a polarized CFTR distribution on the membrane of hAECs cultured in SAGM, similar to that observed in polarized airway cells in vivo. Further, hAECs induced to express CFTR possessed functional iodide/chloride (I(-/)Cl(-)) ion channels that were inhibited by the CFTR-inhibitor CFTR-172, indicating the presence of functional CFTR ion channels. These data suggest that hAECs may be a promising source for the development of a cellular therapy for cystic fibrosis.
authors.affiliation: The Ritchie Centre, Monash Institute for Medical Research, Monash University, Melbourne, Australia.
authors.forename: Sean V
authors.initials: SV
authors.lastname: Murphy
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.forename: Philip
authors.initials: P
authors.lastname: Heraud
authors.forename: Marian
authors.initials: M
authors.lastname: Cholewa
authors.forename: Mark
authors.initials: M
authors.lastname: Le Gros
authors.forename: Martin D
authors.initials: MD
authors.lastname: de Jonge
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Howard
authors.forename: David
authors.initials: D
authors.lastname: Paterson
authors.forename: Courtney
authors.initials: C
authors.lastname: McDonald
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
mesh_terms: D000650:Amnion / Q000166:cytology*; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007455:Iodine / Q000378:metabolism; D021381:Protein Transport; D015533:Transcriptional Activation
chemical_list: C505032:CFTR protein, human; D003470:Culture Media; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D007455:Iodine