An introduction to Research | Current research funded by CLDF | Hepatic progenitor cells as a solution to re-populating the failing human liver

Hepatic progenitor cells as a solution to re-populating the failing human liver

Hepatic progenitor cells as a solution to re-populating the failing human liver: an achievable objective with realistic therapeutic potential?

Dr R Joplin - Institute of Biomedical Research, University of Birmingham Medical School

Liver has the remarkable ability to re-grow after surgical removal of up to 2/3 of its mass. Remaining cells divide and re-organise themselves to restore the original size, shape and composition of the organ. The renewal process is thought to be controlled by signals from cells and molecules in the remaining undamaged portion of liver. Most human liver diseases however have a prolonged (chronic) duration and scar tissue (fibrosis) forms and replaces the normal liver structure. In fibrotic liver, new immature cells are formed but these cells fail to develop fully into mature, normally functioning liver tissue. We have found that immature cells are able to mature if they are removed from the damaged liver and grown in an experimental model of the normal liver environment. These studies suggest that damaged liver contains factors that prevent restoration of a functioning liver. Stem cell therapy has been suggested for treatment of chronic liver diseases; stem cells would be used to re-populate the diseased liver.  However, our studies suggest that this treatment might fail because the environment in the chronically diseased liver is hostile to the immature cells that form. We propose to use our experimental model of the liver environment to investigate the properties of immature liver cells and stem cells and the factors that influence their ability to form an intact liver.  In the longer term such studies may help us to decide which cell types and conditions are likely to be successful in re-populating the chronically failing liver and may also form a basis for development of an improved artificial liver. Such a device might be applicable specifically to paediatric patients because of the relatively smaller size of the unit that would be required and because the livers of children contain relatively a higher proportion of stem cells.

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