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Title: Haematopoietic stem cell response in alcohol induced liver injury
Author: Dalakas, E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Aims: 1) To investigate the mobilisation and hepatic recruitment of HSCs in patients with alcohol induced liver injury and define their contribution to parenchymal and nonparenchymal liver cell lineages. 2) To establish that mobilised HSCs in alcohol induced liver injury are functional and demonstrate pluripotent stem cell properties. 3) To study the role of inflammatory cytokines and chemokine axes in regulating the mobilisation and hepatic recruitment of HSCs in alcohol induced liver injury. Methods: Liver biopsies from alcoholic hepatitis (AH) patients and male patients who had received a female liver transplant (and who subsequently developed AH) were analysed for HSC content using immunohistochemical and flurorescent in situ hybridisation techniques (FISH). FISH for Y-chromosome was performed on liver tissue, along with co-staining for hepatocyte, biliary, myofibroblasts (α-SMA) and hepatic parenchymal cells proliferation markers. Peripheral blood HSC (CS34+) levels were quantified in AH patients and normal controls (NC) using flow cytometry and CD34+/CD45+ HSCs were collected and cultured in colony forming unit (CFU) assays. CXCR3/CXCR4 receptor cell expression on mobilised CD34+ HSCs were quantified in AH patients using flow cytometry. Conclusions: Alcohol induced liver injury mobilises CD34+ stem cells into the peripheral circulation and recruits them into the liver. These bone marrow derived stem cells contribute to the hepatic myofibroblasts population but not to parenchymal lineages and their presence within the liver does not promote hepatocyte repair. Mobilised HSCs from AH patients were functional and displayed true stem cell potential at a level higher than control HSCs. Serum SDF-1, MMP-9 and G-CSF rather than chemokine receptor expression, plays a central role in regulating the mobilisation of CD34+ stem cells in alcohol induced liver injury.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available