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Investigating Human Oesophageal Epithelial Stem-Progenitor Cells and their Ability to Reconstruct a Functional Epithelium within a Tissue Engineered Oesophagus

Phylactopoulos, Demetra-Ellie; (2019) Investigating Human Oesophageal Epithelial Stem-Progenitor Cells and their Ability to Reconstruct a Functional Epithelium within a Tissue Engineered Oesophagus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Reconstructing an oesophagus through tissue engineering might be beneficial for patients suffering from a broad spectrum of oesophageal diseases, both congenital and acquired. ‘Long-gap’ oesophageal atresia is a congenital malformation, where the oesophagus does not properly develop, creating a gap between the proximal and distal parts. Regenerative medicine may offer a therapeutic alternative to these patients by combining biomaterials with bona fide stem cells to create a suitable oesophageal replacement. In order to rebuild a functional oesophageal replacement, all the structural features of the oesophageal layers need to be regenerated in vivo. This study focuses on the underlying biology of human oesophageal epithelial cells (HuOEC) and their ability to reconstruct a functional stratified epithelium within a tissue engineered oesophagus. In particular, I have (i) established the conditions necessary for HuOEC to extensively expand in vitro, while maintaining their capacity to differentiate, (ii) assessed HuOEC clonogenicity using single-cell analysis and identified different clonogenic populations within the oesophageal epithelium, (iii) studied the development of human foetal oesophageal epithelium to understand its morphogenesis and maintenance and (iv) succeeded in the reconstitution of an epithelium barrier ex vivo and in vivo using cultivated oesophageal epithelial cells, derived both from rat and human samples, over a decellularised extracellular matrix. Importantly, oesophageal epithelial cells are able to give rise to a squamous stratified epithelium on a xenogeneic extracellular matrix that resembles the native oesophageal epithelium. The newly reconstructed epithelium maintains a subpopulation of epithelial cells with proliferation capacity and clonogenic potential, thus supporting their stem/progenitor identity. The results that will be presented include part of the extensive characterisation of HuOEC, the feasibility of engineering a human oesophageal replacement with mucosal barrier function and suggest the existence of oesophageal epithelial clonogenic and self-renewing stem cells.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating Human Oesophageal Epithelial Stem-Progenitor Cells and their Ability to Reconstruct a Functional Epithelium within a Tissue Engineered Oesophagus
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
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 Medical Sciences
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
URI: https://discovery.ucl.ac.uk/id/eprint/10088176
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