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The isolation, characterisation and culture of putative human liver progenitor cells

Laurson, J; (2006) The isolation, characterisation and culture of putative human liver progenitor cells. Doctoral thesis , UCL (University College London). Green open access

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Abstract

The aim of this thesis was to investigate diseased human livers for the presence of liver progenitors. There is a shortage of organ donors and the difficulty in treating acute and chronic liver diseases puts emphasis on the need for alternative therapies to orthotopic liver transplants. The long term aim is to find a cell source which could populate a bio-artificial liver device. Liver stem cells would have the capacity to expand into large enough numbers needed for such a device and to differentiate into functional liver cells. Non-parenchymal cells were isolated from human liver, notably from livers explanted from patients with acute liver failure or cirrhosis. The underlying hypothesis was that livers removed at transplantation would be enriched in hepatocyte progenitors as they are trying to regenerate and repair the damaged tissue. Putative liver progenitor colonies were identified and characterised by (a) culture of non-parenchymal cells and observation for adoption of a mature hepatocyte phenotype and (b) assayed for the presence of stem cell and mature liver cell lineage markers (hepatocytes and biliary epithelial cells). Markers were investigated using RT-PCR, immunocytochemistry (on cytospins and in-situ in culture wells) and FACS analysis. Markers studied included c- met (HGF-receptor), CD49f (a6-integrin), haematopoietic stem cell markers CD117 and CD 133, and multidrug resistance protein ABCG2/BCRP. Proliferating colonies were also manipulated by immortalisation (hTERT) and cultured with either growth factors thought to be likely to induce hepatocyte proliferation and/or factors associated in differentiation.

Type: Thesis (Doctoral)
Title: The isolation, characterisation and culture of putative human liver progenitor cells
Identifier: PQ ETD:592980
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/1445656
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