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Type: Thesis
Title: Mesenchymal stem cells in an ovine model of kidney transplantation
Author: Lett, Bron Douglas
Issue Date: 2018
School/Discipline: Adelaide Medical School
Abstract: Mesenchymal stem cells (MSCs) have the potential to address current issues in transplantation with their immunosuppressive and regenerative abilities. MSCs as a therapy to improve kidney transplant outcomes have already been taken to the clinical trial stage. The results of these trials have, unfortunately, been disappointing with no significant improvements seen over current transplant outcomes. A return to basic science will help to answer many of the questions surrounding the best methods for the use of MSCs in transplantation medicine. To this end this thesis has set out to examine the application of MSCs in a sheep model of heterotopic kidney transplantation. Chapter 3 describes the isolation, characterisation, and labelling of MSCs with a superparamagnetic iron oxide (SPIO) nano particle that can be used to track the cells using MRI and Prussian blue staining. Importantly, labelling the cells with the SPIO did not have an impact on their phenotype or function. In Chapter 5, the SPIO-MSCs then had their migration tracked when delivered systemically in a sheep kidney autotransplantation model, the development of which is described in chapter 4. The observations indicated the cells passed through the transplanted kidney at 15 minutes post administration but had dispersed by 30 minutes. Upon histological study, significantly more cells had been found to localize to the transplanted kidney than to the native kidney. Lastly, chapter 6 details the effects of MSCs delivered into the artery of kidney allografts. Looking at the creatinine, urea, and kim-1 levels of sheep early after transplantation and later undergoing rejection, gave suggestions that MSCs could reduce kim-1 levels soon after transplantation and may reduce some aspects of rejection. Additionally, the MSCs did not negatively impact the transplanted kidney, demonstrating the safety of delivering the cells arterially.
Advisor: Coates, Toby
Drogemuller, Chris
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2018
Keywords: Stem cells
kidney transplantation
animal model
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
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