Perin, Silvia;
(2019)
Precursors of “Enteric” Smooth Muscle: from developmental origin to regenerative medicine.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
A tissue-engineered intestine could be the ideal solution to overcome two of the main constrains of transplantation, such as donor shortage and life-long immunosuppression, to treat intestinal failure in children and in adults. In order to build a functional intestine, all its layers need to be regenerated. Unfortunately, while the precursors of the epithelium and the enteric nervous system have been already identified, the origin of intestinal smooth muscle cells is still undetermined. Thus, the purpose of my research was twofold: i) investigate the origin of smooth muscle cells during mouse and human intestinal development to identify putative smooth muscle precursors; ii) isolate and characterise intestinal mesoangioblasts as a vascular source of smooth muscle cells for regenerative use. In this study, a population of cells co-expressing cKit and PDGFRα was identified as the putative smooth muscle precursor population using immunofluorescence and RNA-sequencing techniques at different developmental stages. Intestinal mesoangioblasts were successfully isolated from foetal and paediatric intestinal biopsies and showed similarities with pericytes. Upon different treatments mesoangioblasts were able to differentiate into smooth muscle cells as confirmed by immunofluorescence, western blotting, qPCR and transcriptome analyses. Moreover, cells showed an innate differentiation potential towards smooth muscle in vivo. When seeded into decellularised foetal midguts, mesoangioblasts successfully regenerated two orthogonal smooth muscle layers resembling the native layers. Overall, the work reported in this PhD provided new insights into the origin of the longitudinal smooth muscle layer of the gut and identified in intestinal mesoangioblasts a source of smooth muscle precursors, that can be easily isolated from intestinal biopsies and can be used in regenerative medicine.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Precursors of “Enteric” Smooth Muscle: from developmental origin to regenerative medicine |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| 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 > 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 Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10088260 |
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