|dc.description.abstract||The liver has the ability to regenerate rapidly during acute liver injury by activating
mature hepatocytes to divide and restore the damaged liver mass. In contrast, the
liver relies on hepatic progenitor cells (HPCs) which have the ability to differentiate
into both hepatocytes and biliary cells for regeneration during chronic liver injuries.
Whole organ transplant is the most effective treatment for end stage liver diseases.
However, there is a constant shortage of donor organs causing the death of many
patients while waiting for suitable donor organs. HPC transplant is a potential
alternative for whole organ transplant. However the isolation of HPC which is scarce
in the liver and the expansion of these cells to a number that is suitable for transplant
have been challenging.
To investigate the plausibility of using HPCs as an alternative for liver transplant, I
developed a protocol to isolate and expand HPC in vitro. Using this system, I
investigated the complex hierarchy of HPCs in aid to select a defined population of
HPC that is suitable for transplant. I found the EpCAM+ CD24+ population marks a
naïve population of HPC that might be suitable for cell therapy.
I further investigate the liver repopulating capacities of these cells by isolating
EpCAM+CD24+ HPC population by Fluorescence Activated Cell Sorting (FACS)
from a hepatocellular injury model. Surprisingly, a subpopulation of the EpCAM+
CD24+ HPCs which are also CD133+ possesses a higher colony forming capacities
has been identified. Most importantly, this population can be expanded to a large
scale in vitro and able to repopulate the injured liver after transplant.
This defined population of HPCs can also be isolated from a mouse model of fatty
liver disease and the isolated HPCs can be expanded in vitro. These cells are able to
repopulate the liver after cell transplantation. The presence of HPCs that are capable
of being isolated from the fatty liver proved the potential of using HPCs for
transplant in a clinical setting by using cells isolated human fatty liver that are from
rejected for transplant to overcome the shortage of donor organs.||en
|dc.contributor.sponsor||Medical Research Council (MRC)||en
|dc.publisher||The University of Edinburgh||en
|dc.relation.hasversion||Bird TG, Lu WY, Boulter L, Gordon-Keylock S, Ridgway RA, Williams MJ, et al. Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling. Proceedings of the National Academy of Sciences of the United States of America. 2013 Apr 16;110(16):6542-7. PubMed PMID: 23576749. Pubmed Central PMCID: 3631632.||en
|dc.relation.hasversion||Boulter L, Lu WY, Forbes SJ. Differentiation of progenitors in the liver: a matter of local choice. The Journal of clinical investigation. 2013 May 1;123(5):1867-73. PubMed PMID: 23635784. Pubmed Central PMCID: 3635730.||en
|dc.title||Defining the liver repopulating capacities of hepatic progenitor cells||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en