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dc.contributor.advisorForbes, Stuarten
dc.contributor.advisorWigmore, Stephenen
dc.contributor.authorStutchfield, Benjamin Marken
dc.date.accessioned2017-04-20T13:38:35Z
dc.date.available2017-04-20T13:38:35Z
dc.date.issued2015-07-04
dc.identifier.urihttp://hdl.handle.net/1842/21686
dc.description.abstractAcute liver failure confers a high risk of death, with liver transplantation offering the only effective therapy for life-threatening cases. Hepatic macrophages are crucial for innate immune integrity and effective hepatocyte proliferation. The macrophage may therefore present a novel therapeutic target to enhance regeneration following acute liver injury. In this thesis I describe the development and use of mouse models of liver injury including partial hepatectomy, partial hepatectomy plus chronic liver injury and paracetamol intoxication. I show the development of liver function assays in these models including quantification of hepatic clearance of indocyanine green by fluorescent imaging and assessment of hepatic phagocytic capacity using fluorescent microbeads. I then describe macrophage based therapeutic interventions in mouse models of liver injury. Firstly the direct administration of bone marrow derived macrophages in partial hepatectomy plus chronic liver injury. I then tested the administration of macrophage colony stimulating factor in mouse models of partial hepatectomy, partial hepatectomy plus chronic liver injury and paracetamol intoxication, describing the phenotype and exploring mechanisms of action. Collaborating with others I assessed serum CSF1 levels in humans with liver injury due to partial hepatectomy or paracetamol intoxication. I show that in acute liver failure a high serum CSF1 level is predictive of survival, indicating a new mechanistic biomarker.en
dc.contributor.sponsorWellcome Trusten
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionStutchfield, B.M., Forbes, S.J. & Wigmore, S.J. Prospects for stem cell transplantation in the treatment of hepatic disease. Liver Transpl 16, 827-836 (2010).en
dc.relation.hasversionStutchfield, B.M., Rashid, S., Forbes, S.J. & Wigmore, S.J. Practical barriers to delivering autologous bone marrow stem cell therapy as an adjunct to liver resection. Stem Cells Dev 19, 155-162 (2010).en
dc.relation.hasversionWigmore SJ, Stutchfield BM, Forbes SJ. Liver Functions and Failure. In. Garden OJ, Parks RW. Companion to Specialist Surgical Practice: Hepatobiliary and Pancreatic Surgery, 5/e.2014en
dc.relation.hasversionMoore, J.K., Stutchfield, B.M. & Forbes, S.J. Systematic review: the effects of autologous stem cell therapy for patients with liver disease. Aliment Pharmacol Ther 39, 673-685 (2014).en
dc.relation.hasversionStutchfield, B.M. & Forbes, S.J. Liver sinusoidal endothelial cells in disease - And for therapy? J Hepatol 58, 178-180 (2013).en
dc.relation.hasversionFallowfield J, Hayden A, Snowdon V, Aucott R, Stutchfield BM, Mole D, Pellicoro A, Gordon-Walker T, Henke A, Schrader J, Trivedi P, Princivalle M, Fores S, Collins J, Iredale J. Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo. Hepatology, 59(4): 1492-504, 2014en
dc.subjectliveren
dc.subjectmacrophageen
dc.subjectregenerationen
dc.titleManipulating macrophages to enhance liver regenerationen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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