Trans-differentiation is the term applied where one fully differentiated cell type changes into another fully differentiated cell type. The AR432J-B13 cell line has been shown to demonstrate this phenomenon in vitro. These cells of exocrine pancreatic lineage, can trans-differentiate into hepatocytes upon treatment with the synthetic glucocorticoid dexamethasone. This thesis demonstrates that the generation of these cells (B13-H) from AR42J-B13 cells could prove to be a novel source of hepatocytes in culture. B13-H cells express functionally active and inducible CYP enzymes for at least 30 days in culture, an attribute that primary hepatocytes do not hold. In addition, B13-H cells have shown to be a useful alternative to primary hepatocytes in the investigation of protective mechanisms against paracetamol toxicity. The pancreas and liver have a close association developmentally which helps to explain their relationship in adulthood. As primary hepatocytes rapidly dedifferentiate in culture, the use of these or other pancreas-derived hepatocytes would be beneficial, both in a clinical (e.g. bioartificial liver device as a 'bridge' until transplant) and pharmacological (e.g. drug metabolism studies) settings. Another liver cell affected by disease is the hepatic stellate cell. These cells trans-differentiate into a myofibroblast-like cell and are pivotal in the formation of liver fibrosis. By inhibiting this trans-differentiation event, liver fibrosis can resolve, thereby preventing the terminal state of cirrhosis. PCN is such a compound capable of achieving this outcome both in vitro using isolated hepatic stellate cells and in vivo carbon tetrachloride-induced rodent liver-injury models. Transgenic mice enabled the determination that this effect is both dependent and independent upon the nuclear receptor PXR of which PCN is a ligand.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:408956 |
| Date | January 2004 |
| Creators | Marek, Carylyn Jane |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU186421 |
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