Buck, H;
(2021)
Enhancing stem cell engraftment and function following corneal stem cell transplantation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Transplantation of limbal epithelial stem cells (LESCs) can be an effective treatment for patients with Limbal Stem Cell Deficiency (LSCD), a condition where loss or damage of corneal stem cells results in painful inflammation and blindness. However, failure rates of both auto- and allografted cultured LESCs are high despite systemic immune suppression, for which the reasons are unclear. This project aimed to investigate variables important for successful engraftment, including graft stem cell composition, the graft bed inflammatory microenvironment, and the role of the immune system in corneal epithelial graft rejection. We developed a mouse model of LSCD induced by chemical injury, able to accurately recapitulate features of the LSCD phenotype seen in human patients including corneal haze, epithelial defects, and neovascularisation accompanied by significant cellular infiltration into the cornea. We also demonstrated successful regeneration of the LSCD injury by transplanting sheets of corneal epithelium containing LESCs, while tracking engraftment and growth kinetics during wound healing. Transplant of allogeneic donor derived epithelial grafts demonstrated characteristic signs of graft rejection including significant cellular infiltration into the cornea and expression of inflammatory cytokines and chemokines. Adoptive transfer of fluorescently labelled purified allogeneic immune cell subsets, including CD4+ and CD8+ T cells, to immunodeficient transplant recipients demonstrated their effect on stable epithelial grafts in vivo. This project also aimed to develop strategies for the isolation and enrichment of LESC from primary human corneas. Several methods of tissue digestion and LESC isolation were compared, and the inflammatory chemokine and cytokine profile of primary human corneal epithelial and stromal cells was investigated in vitro.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Enhancing stem cell engraftment and function following corneal stem cell transplantation |
| Event: | UCL |
| 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 > 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 Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10139528 |
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