Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116759
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Type: Journal article
Title: Epithelial disruption: a new paradigm enabling human airway stem cell transplantation
Author: Farrow, N.
Cmielewski, P.
Donnelley, M.
Rout-Pitt, N.
Moodley, Y.
Bertoncello, I.
Parsons, D.
Citation: Stem Cell Research and Therapy, 2018; 9(1):153-1-153-8
Publisher: BioMed Central
Issue Date: 2018
ISSN: 1757-6512
1757-6512
Statement of
Responsibility: 
Nigel Farrow, Patricia Cmielewski, Martin Donnelley, Nathan Rout-Pitt, Yuben Moodley, Ivan Bertoncello and David Parsons
Abstract: Background: 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.
Keywords: Stem cells; airways; transplantation; gene therapy
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.
RMID: 0030090588
DOI: 10.1186/s13287-018-0911-4
Grant ID: http://purl.org/au-research/grants/nhmrc/1098127
Appears in Collections:Medicine publications

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