Development of stem cell-derived hepatocyte models



Pridgeon, CS
(2019) Development of stem cell-derived hepatocyte models. PhD thesis, University of Liverpool.

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Abstract

Stem cell derived models of hepatocytes have potential in toxicity testing and regenerative medicine. Despite global efforts drug-induced liver-injury (DILI) remains a major concern for the pharmaceutical and healthcare industries and is a considerable cause of morbidity and mortality. Therefore, efforts are being made to reduce its incidence through toxicity screening to prevent the release of unsafe compounds to market. Current models of DILI are flawed, either lacking in terms of physiological relevance in the case of hepatic cell lines or in terms of reproducibility and availability in the case of human primary hepatocytes (hPH). Stem cell-derived hepatocyte models offer a theoretically unlimited source of potentially high-quality hepatocytes for toxicity testing. However, currently they are hindered by lack of maturity compared with hPH as in the case of pluripotent stem cell-derived hepatocyte-like cells (PSC-HLCs), or are incompletely phenotyped, in the case of human liver organoids. Hypoxic conditions improve the stemness of PSCs, in addition, during embryogenesis cells are exposed to hypoxic conditions. Furthermore, there is a range of oxygen concentration across the liver lobule which is implicated ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User: Symplectic Admin
Date Deposited: 07 Jan 2020 15:10
Last Modified: 03 Apr 2025 04:56
DOI: 10.17638/03060785
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3060785