The role of stem cells in progressive liver injury.
Background: There has been a recent explosion of research in the area of both general and liver stem cell biology and this has led to considerable debate about the origin and function of hepatic stem cells. The term, “plasticity” has been coined to emphasize the process in which pluripotent stem cells are able to differentiate into multiple cell lineages, and is supported by the finding of intrahepatic chimerism in transplant recipients as well as the apparent repopulation of injured livers with bone marrow derived cells. The term, “transdifferentiation”, is used to focus on differentiation of cells from one organ specific lineage to those of another organ. These concepts have an underlying assumption, which is not proven, that there are distinct liver specific stem cell precursors that are important in liver regeneration following injury (1). Hypothesis and aims: Our working hypothesis is that liver injury recruits/mobilises circulating and bone marrow stem cell populations that are specific for the liver. We aim to address this hypothesis by examining isolated circulating and bone marrow stem populations from both mice and humans with liver disease and non-diseased controls. Further, we plan to focus on the role of the hedgehog pathway in hepatic stem cell recruitment as well as using functional genomics approaches, including gene arrays and microRNA arrays, to better understand the process of endothelial mesenchymal transition (EMT). Conclusion and Significance: This project has great significance in determining the nature of the stem cell response in liver injury. Indeed the results will have widespread implications for the majority of human disease, as this is likely to be general stem cell response. This project embodies a number of techniques and builds on established knowledge and expertise with our laboratory. We look forward to attracting a student to what we believe is exciting and significant work! 1. N. A. Shackel and D. C. Rockey (2005) In pursuit of the "Holy Grail"- Stem cells, hepatic injury, fibrogenesis and repair. Hepatology 41(1) p16-8.
The opportunity ID for this research opportunity is 135