Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713995
Title: Stem cell culture on 3D-scaffolds for cardiac regenerative medicine and in vitro studies
Author: Bruyneel, Arne A. N.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Abstract:
Most life years lost due to death and disability in the Western world arise from non-communicable diseases, such as cancer and cardiovascular disease. Myocardial infarction (MI) and heart failure (HF) still have a particular poor prognosis, despite the development of improved pharmacological therapy and surgical interventions. No cure, other than heart transplant, is available for patients with HF. As a result, further research into new treatment strategies is paramount. Many potential avenues have been suggested, but this thesis aimed to work towards using stem cells and tissue engineering strategies as tool for in vitro testing and in vivo therapy. In the first place, the thesis aimed to develop a humanised Langendorff perfused heart as an in vitro testbed. The decellularised rat heart was chosen as biomaterial, because it allows perfusion, and cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPS) as cell source. Given the size of the constructs and to enable biomimetic mechano-electrical stimulation of the organoids, which may aid in the differentiation and maturation of the cardiomyocytes, a bioreactor was constructed for culturing the recellularised hearts. Finally, the feasibility and performance of culturing decellularised hearts seeded with iPS-CMs in the bioreactor under biomimetic conditions was assessed. The performance of this technique was currently insufficient for it to be used as an in vitro model of the heart. Hence, further improvements in bioreactor design and cell culture technique are required. Secondly, the therapeutic benefit of a cell-loaded collagen scaffold was investigated in a rat ischaemia-reperfusion myocardial infarction (MI) model. A bilayer collagen scaffold was designed for this purpose and biocompatibility demonstrated both in vivo and in vitro. Cardiosphere-derived stem cells were used as cell source, given their potential to form cardiomyocytes and blood vessel structures, and their therapeutic benefit post-MI. In the present study, the cells were pre-conditioned with hypoxia, as this increased stemness and pro-angiogenic factor secretion, before implantation post-MI. However, a twelve week study using magnetic resonance imaging to study cardiac function failed to show significant improvements in function post-MI. In summary, this thesis contributed to the development of technology for both in vitro and in vivo cardiac tissue engineering. However, further investigation and optimisation will be required before this technology can be applied in practice.
Supervisor: Carr, Carolyn ; Tyler, Damian Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.713995  DOI: Not available
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