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Human Amnion Epithelial Cells Induced to Express Functional Cystic Fibrosis Transmembrane Conductance Regulator

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [4];  [5];  [6];  [6];  [6];  [7];  [8];  [2];  [2]
  1. Monash Univ., Melbourne, VIC (Australia). Monash Inst. for Medical Research. The Ritchie Centre; DOE/OSTI
  2. Monash Univ., Melbourne, VIC (Australia). Monash Inst. for Medical Research. The Ritchie Centre; Monash Univ., Melbourne, VIC (Australia). Dept. of Obstetrics and Gynaecology
  3. Monash Univ., Melbourne, VIC (Australia). School of Chemistry. Centre for Biospectroscopy
  4. Monash Univ., Melbourne, VIC (Australia). Monash Centre for Synchrotron Science
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division
  6. Australian Synchrotron, Melbourne, VIC (Australia). X-ray Fluorescence Microscopy
  7. Monash Univ., Melbourne, VIC (Australia). Monash Inst. for Medical Research. The Ritchie Centre
  8. Wake Forest Univ., Winston-Salem, NC (United States). School of Medicine. Wake Forest Inst. for Regenerative Medicine
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 (I2/ Cl2) 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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627554
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 9 Vol. 7; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (24)

CFTR-Mediated Anion Conductance Regulates Na+-K+-Pump Activity in Calu-3 Human Airway Cells journal July 2000
CFTR Regulation of Intracellular Calcium in Normal and Cystic Fibrosis Human Airway Epithelia journal October 2000
Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis journal December 2002
The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions journal March 2002
Gene and cell therapy for cystic fibrosis: From bench to bedside journal June 2011
Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms journal November 1997
Mislocalization of ΔF508 CFTR in cystic fibrosis sweat gland journal August 1992
Phosphorylation of CFTR by PKA promotes binding of the regulatory domain journal July 2005
Gene therapy for cystic fibrosis: an example for lung gene therapy journal September 2004
Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans journal October 2009
Ordered subsets algorithms for transmission tomography journal October 1999
Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia journal May 2005
Stem Cells Derived from Human Fetal Membranes Display Multilineage Differentiation Potential journal September 2007
Advances in cystic fibrosis gene therapy journal November 2004
Regularization for uniform spatial resolution properties in penalized-likelihood image reconstruction journal June 2000
A Decade of CLC Chloride Channels: Structure, Mechanism, and Many Unsettled Questions journal June 2000
Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells journal January 2012
Human Amnion Epithelial Cell Transplantation Abrogates Lung Fibrosis and Augments Repair journal September 2010
CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney journal March 2006
Development of a Colorimetric Method for Functional Chloride Channel Assay journal October 2004
Common Gene Therapy Viral Vectors Do Not Efficiently Penetrate Sputum from Cystic Fibrosis Patients journal May 2011
Human Amniotic Epithelial Cells as Novel Feeder Layers for Promoting Ex Vivo Expansion of Limbal Epithelial Progenitor Cells journal May 2007
Cystic Fibrosis, Vector-Mediated Gene Therapy, and Relevance of Toll-Like Receptors: A Review of Problems, Progress, and Possibilities journal June 2008
Human Amnion Epithelial Cells Prevent Bleomycin-Induced Lung Injury and Preserve Lung Function journal July 2011

Cited By (8)

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?: Fetal Membranes in Regenerative Medicine journal August 2017
Efficient Gene Editing at Major CFTR Mutation Loci journal June 2019
Maintenance of human amnion epithelial cell phenotype in pulmonary surfactant journal January 2014
Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs journal March 2017
Endogenous and Exogenous Stem/Progenitor Cells in the Lung and Their Role in the Pathogenesis and Treatment of Pediatric Lung Disease journal April 2016
Amnion Epithelial Cells Promote Lung Repair via Lipoxin A4 journal November 2016
A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery: Tunable Hydrogel for Cytokine Release and Cell Delivery
  • Skardal, Aleksander; Murphy, Sean V.; Crowell, Kathryn
  • Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 105, Issue 7 https://doi.org/10.1002/jbm.b.33736
journal June 2016
Cell therapy for cystic fibrosis: Cell therapy for cystic fibrosis journal July 2013

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