Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116759
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dc.contributor.authorFarrow, N.en
dc.contributor.authorCmielewski, P.en
dc.contributor.authorDonnelley, M.en
dc.contributor.authorRout-Pitt, N.en
dc.contributor.authorMoodley, Y.en
dc.contributor.authorBertoncello, I.en
dc.contributor.authorParsons, D.en
dc.date.issued2018en
dc.identifier.citationStem Cell Research and Therapy, 2018; 9(1):153-1-153-8en
dc.identifier.issn1757-6512en
dc.identifier.issn1757-6512en
dc.identifier.urihttp://hdl.handle.net/2440/116759-
dc.description.abstractBackground: Airway disease is a primary cause of morbidity and early mortality for patients with cystic fibrosis (CF). Cell transplantation therapy has proven successful for treating immune disorders and may have the potential to correct the airway disease phenotype associated with CF. Since in vivo cell delivery into unconditioned mouse airways leads to inefficient engraftment, we hypothesised that disrupting the epithelial cell layer using the agent polidocanol (PDOC) would facilitate effective transplantation of cultured stem cells in mouse nasal airways. Methods: In this study, 4 μL of 2% PDOC in phosphate-buffered saline was administered to the nasal airway of mice to disrupt the epithelium. At 2 or 24 h after PDOC treatment, two types of reporter gene-expressing cells were transplanted into the animals: luciferase-transduced human airway basal cells (hABC-Luc) or luciferase-transduced human amnion epithelial cells (hAEC-Luc). Bioluminescence imaging was used to assess the presence of transplanted luciferase-expressing cells over time. Data were evaluated by using two-way analysis of variance with Sidak's multiple comparison. Results: Successful transplantation was observed when hABCs were delivered 2 h after PDOC but was absent when transplantation was performed 24 h after PDOC, suggesting that a greater competitive advantage for the donor cells is present at the earlier time point. The lack of transplantation of hAECs 24 h after PDOC supports the importance of choosing the correct timing and cell type to facilitate transplantation. Conclusions: These studies into factors that may enable successful airway transplantation of human stem cells showed that extended functioning cell presence is feasible and further supports the development of methods that alter normal epithelial layer integrity. With improvements in efficacy, manipulating the airway epithelium to make it permissive towards cell transplantation may provide another option for safe and effective correction of CF transmembrane conductance regulator function in CF airways.en
dc.description.statementofresponsibilityNigel Farrow, Patricia Cmielewski, Martin Donnelley, Nathan Rout-Pitt, Yuben Moodley, Ivan Bertoncello and David Parsonsen
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rights© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectStem cells; airways; transplantation; gene therapyen
dc.titleEpithelial disruption: a new paradigm enabling human airway stem cell transplantationen
dc.typeJournal articleen
dc.identifier.rmid0030090588en
dc.identifier.doi10.1186/s13287-018-0911-4en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1098127en
dc.identifier.pubid424816-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS14en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidFarrow, N. [0000-0002-2289-1268]en
dc.identifier.orcidCmielewski, P. [0000-0002-2236-9410]en
dc.identifier.orcidDonnelley, M. [0000-0002-5320-7756]en
dc.identifier.orcidRout-Pitt, N. [0000-0002-4003-4454]en
dc.identifier.orcidParsons, D. [0000-0003-1746-3290]en
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