Meran, Lawen;
(2021)
Bioengineering Functional Human Jejunal Grafts for Intestinal Failure.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Intestinal failure (IF), following extensive anatomical or functional loss of small intestine, has debilitating long-term effects on infants born with this condition. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to improve nutritional independence. Children with irreversible IF suffering complications of parenteral nutrition may be referred for intestinal transplantation. However, mortality rates are as high as 60% at 5 years. The aim of my project was to develop an innovative treatment strategy to rebuild the patients’ own jejunum for autologous transplantation. Here I report the reconstruction of transplantable intestinal mucosal grafts using primary human materials. Human jejunal intestinal organoids derived from paediatric patients with IF can be cultured and expanded efficiently in vitro with region-specific markers preserved. Decellularised human intestinal matrix with intact ultrastructure is used as biological scaffold. I show that the biochemical composition of decellularised human small intestine and colon matrix are virtually analogous, suggesting that they both can be used as scaffolds for jejunal graft reconstruction. Functional jejunal grafts with digestive enzyme-producing enterocytes can be efficiently engineered by repopulating human intestinal scaffolds with human jejunal organoids and fibroblasts in vitro, which can further survive and mature after in vivo transplantation. These primary human material based jejunal grafts provide proof-of-concept data for autologous transplantation of tissue engineered intestine in patients with IF.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Bioengineering Functional Human Jejunal Grafts for Intestinal Failure |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/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 Population Health 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/10123436 |
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