Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548025
Title: The use of a recombinant single chain antibody in the investigation of liver fibrosis
Author: Marshall, Helen Louise
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2011
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Abstract:
Liver fibrosis is one of the leading causes of morbidity and mortality in the western world and represents a significant burden to the health system. The continued elucidation of the mechanisms governing liver fibrosis has identified the hepatic myofibroblast, derived from quiescent hepatic stellate cells, as the principle cell type involved in disease progression with several studies demonstrating that hepatic myofibroblast apoptosis correlated with attenuated fibrosis severity. A recombinant single chain antibody (scAb), termed C1-3, has been developed and shown to actively target hepatic myofibroblasts expressing synaptophysin both in vitro and in vivo. The aim of this thesis was to use C1-3 (conjugated to an appropriate agent) as an imaging agent; to examine the effect of hepatic myofibroblast depletion on regeneration following two thirds partial hepatectomy (PHx) and to examine if hepatic myofibroblast depletion in a cirrhosis model promotes fibrosis regression. The data in this thesis show that conjugation of C1-3 to a fluorophore provides a novel non invasive method for differentiating between the different stages of carbon tetrachloride induced liver fibrosis in animal models, with increasing hepatic myofibroblast number (determined by αSMA staining) correlating with disease progression. Hepatic myofibroblast depletion prior to and during PHx revealed a complex role for these cells during liver regeneration through the provision of factors that both stimulated and reduced parenchymal cell proliferation. C1-3 mediated-depletion of hepatic myofibroblasts in a sustained model of liver injury revealed that removal of these cells was not sufficient to stimulate fibrosis regression since no difference in collagen deposition was observed. The data in this thesis demonstrate the complex role of hepatic myofibroblasts during liver regeneration and sustained injury and suggest that further studies are required to elucidate the exact mechanisms involved before depletion of hepatic myofibroblasts can be a viable therapeutic option.
Supervisor: Not available Sponsor: Hunter Memorial Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.548025  DOI: Not available
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