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Using a 3D collagen matrix to deliver respiratory progenitor cells to decellularized trachea in vivo

Hamilton, N; Hynds, R; Gowers, K; Tait, A; Butler, C; Hopper, C; Burns, A; ... Janes, SM; + view all (2019) Using a 3D collagen matrix to deliver respiratory progenitor cells to decellularized trachea in vivo. Tissue Engineering Part C: Methods , 25 (2) pp. 93-102. 10.1089/ten.TEC.2018.0241. Green open access

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Abstract

Airway epithelial cells are a key barrier to inhaled toxicants, pollutants and infectious agents. During severe epithelial injury and in transplantation settings, it would be desirable to rapidly reintroduce a functional epithelium through the engraftment of exogenous cells or by promoting host regeneration. However, the three-dimensional surface of the airway and the requirement to maintain airflow using stents, which cause mechanical shear at the tracheal surface, are challenges. Here, we investigate a graft composed of human airway epithelial stem/progenitor cells and lung fibroblasts embedded within a supportive collagen matrix, that would be more resistant to mechanical shear than cells exposed directly to the lumen surface. Cells were combined in a collagen I hydrogel before it was dehydrated into a mechanically stable sheet using RAFTTM absorbers. After 48 hours, KRT5+ spheroids formed and BrdU staining indicated active proliferation. To test whether epithelial cell and fibroblast-containing grafts were able to successfully engraft on a section of trachea in vivo, they were implanted onto re-vascularized, decellularized tracheal scaffolds in a rabbit model. After one week, constructs had engrafted with signs of re-vascularization and keratin-positive cells were found throughout the scaffold. Although the long-term fate of these cells in vivo remains uncertain, we envisage that this strategy could improve host epithelial repair and/or contribute directly to mucosal regeneration.

Type: Article
Title: Using a 3D collagen matrix to deliver respiratory progenitor cells to decellularized trachea in vivo
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/ten.TEC.2018.0241
Publisher version: https://doi.org/10.1089/ten.TEC.2018.0241
Language: English
Additional information: © Nick J.I. Hamilton et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0).
Keywords: Tissue engineering, regenerative medicine, mucosa, airway reconstruction, tracheal transplantation, epithelial cells
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10066573
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