Epithelial disruption: a new paradigm enabling human airway stem cell transplantation
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...
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0911-4 |
| _version_ | 1819090847586582528 |
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| author | Nigel Farrow Patricia Cmielewski Martin Donnelley Nathan Rout-Pitt Yuben Moodley Ivan Bertoncello David Parsons |
| author_facet | Nigel Farrow Patricia Cmielewski Martin Donnelley Nathan Rout-Pitt Yuben Moodley Ivan Bertoncello David Parsons |
| author_sort | Nigel Farrow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T22:30:20Z |
| format | Article |
| id | doaj.art-6e0a5ca029d24cec9546c61078b55b9b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T22:30:20Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-6e0a5ca029d24cec9546c61078b55b9b2022-12-21T18:48:06ZengBMCStem Cell Research & Therapy1757-65122018-06-01911810.1186/s13287-018-0911-4Epithelial disruption: a new paradigm enabling human airway stem cell transplantationNigel Farrow0Patricia Cmielewski1Martin Donnelley2Nathan Rout-Pitt3Yuben Moodley4Ivan Bertoncello5David Parsons6Robinson Research Institute, University of AdelaideRobinson Research Institute, University of AdelaideRobinson Research Institute, University of AdelaideRobinson Research Institute, University of AdelaideSchool of Medicine and Pharmacology, University of Western AustraliaLung Health Research Centre, Department of Pharmacology and Therapeutics, University of MelbourneRobinson Research Institute, University of AdelaideAbstract 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.http://link.springer.com/article/10.1186/s13287-018-0911-4Stem cellsAirwaysTransplantationGene therapy |
| spellingShingle | Nigel Farrow Patricia Cmielewski Martin Donnelley Nathan Rout-Pitt Yuben Moodley Ivan Bertoncello David Parsons Epithelial disruption: a new paradigm enabling human airway stem cell transplantation Stem Cell Research & Therapy Stem cells Airways Transplantation Gene therapy |
| title | Epithelial disruption: a new paradigm enabling human airway stem cell transplantation |
| title_full | Epithelial disruption: a new paradigm enabling human airway stem cell transplantation |
| title_fullStr | Epithelial disruption: a new paradigm enabling human airway stem cell transplantation |
| title_full_unstemmed | Epithelial disruption: a new paradigm enabling human airway stem cell transplantation |
| title_short | Epithelial disruption: a new paradigm enabling human airway stem cell transplantation |
| title_sort | epithelial disruption a new paradigm enabling human airway stem cell transplantation |
| topic | Stem cells Airways Transplantation Gene therapy |
| url | http://link.springer.com/article/10.1186/s13287-018-0911-4 |
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