Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572820
Title: Cardiac stem cell therapy for heart failure
Author: Hsiao, Lien-Cheng
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
Availability of Full Text:
Full text unavailable from EThOS. Please contact the current institution’s library for further details.
Abstract:
Cardiovascular disease is a leading cause of death worldwide and becomes increasingly prevalent in the elderly population. Independent of etiopathogenesis, heart failure CHF) is the final common stage of numerous heart diseases. Cardiac stem cell CCSC) therapy has emerged # as a promising cell-based strategy for treatment ofHF. However, cell replacement is not able to fully restore a structurally damaged myocardium in advanced and end-stage HF. The objective of this project was to test the following hypotheses: that a bioengineered heart extracellular matrix CECM) with preserved intact geometric structure could be generated using ,'#"" ... ~ - decellularization by coronary perfusion; and that autologous CSCs, to repopulate this ECM, could be isolated and expanded from the adult heart, with the caveat that autologous CSCs are depleted and impaired by both aging and chronic dilated cardiomyopathy. This will help to develop a possible therapeutic approach for advanced HF, using a combination of CSCs and engineering technique. Resident CSCs were isolated from explant-derived cells CEDCs) and expanded into cardiosphere-derived cells CCDCs) via cardiosphere formation. The CDCs expressed CSC markers Cc-kit and Sca-l ), pluripotent markers COct3/4 and Sox2), and the cardiac lineage-committed marker (Nkx2.5), and showed clonal expansion, self-renewal, and cardiomyogenic potential in vitro. In tissue engineering experiments, CDCs survived and proliferated within biomaterial alginate scaffolds for up to 7 weeks. An engineered bioartificial ECM scaffold was successfully produced from a whole rat heart using retrograde coronary perfusion and possessed an intact 3D architecture with functionally perfusable vascular network. Compared with ventricles, cultures derived from atria produced significantly higher number of c-kit+ and Sca-I+ CSCs Cc-kit: 13% vs. 3.4%; Sea-I: 82% vs. 53%, respectively) and exhibited greater clonogenic and proliferative capacity. CDCs could be grown from young and aged mice, but the yield of CSCs significantly declined with age, as did cell migration and differentiation potential. In comparison to wild-type mice, atrial-CDCs from dystrophic mice showed no significant differences in CSC subpopulations and characteristics, despite confirmation of cardiac dysfunction using MR!. In conclusion, CDCs could be considered to be a viable cell candidate for cardiac therapy and may be used to treat HF at various stages, in combination with myocardial tissue engineering.
Supervisor: Clarke, Kieran ; Cui, Zhanfeng ; Carr, Carolyn Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.572820  DOI: Not available
Share: