The use of adult hepatic stem cells for the treatment of diabetes, based both on the close
embryological association of the pancreas and liver, and on a putative shared tissue stem
cell, has been proposed by a number of studies. This study investigated the capacity of
hepatic oval cells to differentiate into pancreatic endocrine cells in the presence of
pancreatic mesoderm. The GaIN model of hepatic injury was used to induce oval cell
activation in Male Sprague-Dawley rats. A viable and significant oval cell population
could not however, be isolated and propagated in culture. In order to continue
experimentation, a PHeSC-A2 cell line, derived from normal adult porcine liver, was
cultured with quail pancreatic mesoderm in the GFRM-Ham s F12.ITS culture system.
Cells demonstrating positive immulocalization of the pancreatic markers, insulin and
glucagon, were identified as PHeSC-A2-derived, by visual assessment of their nuclear
morphology. Techniques used to confirm these results and preclude the derivation of the
pancreatic endocrine cells from pancreatic endodermal contamination, proved ineffectual.
The tentative results obtained in this study have lead to the following postulations: firstly,
the PHeSC-A2 cell line may possess a higher level of potentiality than previously
demonstrated; secondly, this potential may be due to the shared embryological origins of
the pancreas and liver, and thirdly, permissive signaling from pancreatic mesoderm may
have the capacity to induce the differentiation of hepatic oval cells into pancreatic
endocrine cells. Further research is required to confirm the results obtained in this study
and to substantiate the aforementioned propositions.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/5858 |
| Date | 02 December 2008 |
| Creators | Augustine, Tanya Nadine |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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