Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator

Sean Murphy, Rebecca Seok Wai Lim, Philip Robert Heraud, Marian Cholewa, Mark A Le Gros, Martin Daly de Jonge, Daryl Howard, David John Paterson, Courtney McDonald, Anthony Atala, Graham Jenkin, Euan Morrison Wallace

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Article numbere46533
Number of pages8
JournalPLoS ONE
Volume7
Issue number9
DOIs
Publication statusPublished - 2012

Cite this

Murphy, Sean ; Lim, Rebecca Seok Wai ; Heraud, Philip Robert ; Cholewa, Marian ; Le Gros, Mark A ; de Jonge, Martin Daly ; Howard, Daryl ; Paterson, David John ; McDonald, Courtney ; Atala, Anthony ; Jenkin, Graham ; Wallace, Euan Morrison. / Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator. In: PLoS ONE. 2012 ; Vol. 7, No. 9.
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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.",
author = "Sean Murphy and Lim, {Rebecca Seok Wai} and Heraud, {Philip Robert} and Marian Cholewa and {Le Gros}, {Mark A} and {de Jonge}, {Martin Daly} and Daryl Howard and Paterson, {David John} and Courtney McDonald and Anthony Atala and Graham Jenkin and Wallace, {Euan Morrison}",
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Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator. / Murphy, Sean; Lim, Rebecca Seok Wai; Heraud, Philip Robert; Cholewa, Marian; Le Gros, Mark A; de Jonge, Martin Daly; Howard, Daryl; Paterson, David John; McDonald, Courtney; Atala, Anthony; Jenkin, Graham; Wallace, Euan Morrison.

In: PLoS ONE, Vol. 7, No. 9, e46533, 2012.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Murphy, Sean

AU - Lim, Rebecca Seok Wai

AU - Heraud, Philip Robert

AU - Cholewa, Marian

AU - Le Gros, Mark A

AU - de Jonge, Martin Daly

AU - Howard, Daryl

AU - Paterson, David John

AU - McDonald, Courtney

AU - Atala, Anthony

AU - Jenkin, Graham

AU - Wallace, Euan Morrison

PY - 2012

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