Tissue engineering of human liver
Prof Brian Thomson & Dr Laura Dexter
Nottingham University
2007 – 2010 Postdoctoral Fellowship
The application of tissue engineering to develop three-dimensional models of human liver.
Prof Brian Thomson is Clinical Associate Professor in the School of Molecular Medical Sciences at Nottingham University.
Dr Laura Dexter is a Research Fellow in the Department of Tissue Engineering at Nottingham University.
The purpose of this research is to use the latest tissue engineering techniques to develop three-dimensional models of human liver which will permit both the long-term growth and preservation of function of primary human hepatocytes in vitro. The successful development of an in vitro human liver model would have evident and far reaching consequences for the replacement and reduction of animals in research.
Long-term in vitro culture of functional liver tissue has important implications in three areas of biomedical science: i) in vitro pharmacological screening and hepatotoxicology; ii) the design of bioartificial liver devices for the metabolic support of liver failure; and iii) the development of robust models of human liver disease.
A central limitation in the development of in vitro liver systems has been the early de-differentiation of primary hepatocytes in culture. The Dr Hadwen Trust-funded research project will investigate co-cultures of primary human hepatocytes and hepatic stellate cells grown in three-dimensional spheroids and on complex porous micro-scaffolds. The longevity and differentiated function of hepatocytes maintained on scaffolds will be compared to spheroids. The aim is to develop and validate a robust human liver cell-culture model as a replacement for animal studies.
The use of human liver tissue will directly replace primary rat liver tissue presently used in many tissue engineering models of liver. The development of a human hepatocyte culture which supports viral replication and virion production would replace the use of rodents and non-human primates in many areas of hepatitis research. In addition, human hepatocyte cell systems would be invaluable for pharmacological research and testing, which currently relies heavily on routine tests in rodents.