• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    The role of bone marrow derived cells in cardiac repair 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • The role of bone marrow derived cells in cardiac repair
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • The role of bone marrow derived cells in cardiac repair
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    The role of bone marrow derived cells in cardiac repair

    View/Open
    LOVELLRoleOf2012.pdf (42.48Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    Current pharmacological therapies fail to address the final end-point of cardiac ischaemia — the death and dysfunction of cardiomyocytes. Advances in stem cell biology have provided hope, for the first time, of addressing this underlying pathology. The work performed here was designed to further understanding of the mechanisms by which bone marrow derived cells improve damaged myocardium. In situ hybridisation was used to detect sex chromosomes within ex-planted, human, sex-mismatch hearts. Host derived cells were found at low frequency in donor hearts, suggesting ongoing post-natal cardiac tissue repair. Human mesenchymal stem cells were examined in vitro and in a rat model of ischaemia-reperfusion injury. Cardiomyocytes were not formed when cultured with either 5-azacytidine or ascorbic acid, and the cells failed to home to the ischaemic heart or improve cardiac function. In the same model, rat mononuclear cells significantly reduced infarct size when administered immediately upon reperfusion. Cells were rarely identified within the myocardium. No functional improvement was seen acutely, but at seven days cardiac function had improved. The low frequency of cells retained in the heart suggested that a process other than transdifferentiation accounted for the observations. Hence, evidence for paracrine actions was sought. In the same model, apoptosis and necrosis in cardiomyocytes were found to be significantly reduced. Western blots demonstrated activation of the reperfusion salvage kinase pathway, analogous to that seen in ischaemic pre- and post-conditioning. Blocking this pathway abolished the infarct size reduction. Global proteomic analysis confirmed alterations in protein expression consistent with known cardioprotective pathways. In conclusion, endogenous myocardial repair processes are inadequate to compensate for pathological insults. Supplementation with mononuclear cells in an ischaemia-reperfusion model produced significant benefit to infarct size and cardiac function. The mechanism of benefit appears to be induced by paracrine effects activating pro-survival pathways.
    Authors
    Lovell, Matthew J.
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/2500
    Collections
    • Theses [3600]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.