Partner 8: University of Edinburgh (UEDIN)
The University of Edinburgh is a leading research university. The research assessment exercise (RAE) in 2008 evidenced that 63% of the University’s research activity was in the highest categories (4* and 3*), of which one third is recognized as “world-leading”. The College of Medicine and Veterinary Medicine (CMVM), where the MRC Centre for Regenerative Medicine (CRM) is located, was rated top in the UK for medical research submitted to the hospital-based clinical subjects panel with approximately 70% of its research rated as ‘internationally excellent’ or ‘world leading’. The MRC CRM, is a world-class research centre at the forefront of regenerative medicine with state of the art facilities.
Partner 8 team leader:
Dr David Hay is a PI within the centre and his research focuses on generating high fidelity human hepatocyte models from pluripotent stem cells. These models have been extensively validated and display high levels of metabolic function. The impact of this work has led to numerous plenary presentations and a spin out company, Fibromed Ltd, which is focused on scalable hepatocyte production and delivering highly predictive human liver models for industrial application.
Dr. Hay will lead WP2 to deliver new human iPSC lines and their differentiation down the hepatic lineage. This will include viral reprogramming, cell line establishment, cell line validation and assessment of hepatocellular differentiation capacity. Following the identification of the appropriate iPSC lines, differentiated cells will be produced at scale for transplantation studies.
Over the last decade Dr Hay has been developing models from human pluripotent stem cells. Most recently, Dr Hay embarked on a project with Chemists to identify synthetic polymer matrices with stabilizing properties. These studies identified a game changing synthetic substratum which prolongs hepatocyte viability and improves cell function. Presently, the current state of the art models display metabolic activities and sensitivity which are in line with freshly isolated primary human hepatocytes.
1. Zhou W, et al. (2012) SUMOylation of HNF4α Regulates Protein Stability and Hepatocyte Function. Journal of Cell Science. 125: 3630–3635.
2. Pernagallo S, et al. (2012) Identification of a pro-angiogenic and anti-thrombotic synthetic biopolymer able to acelérate endothelialisation of intra-vascular devices. Advanced Healthcare Materials. 1 (5): 646–656.
3. Hay DC et al. (2011) Unbiased Screening of Polymer Libraries to Define Novel Substrates for Functional Hepatocytes with Inducible Drug Metabolism. Stem Cell Research. 6: 92-101.
4. Sullivan GJ, et al. (2010) Generation of Functional Human Hepatic Endoderm from Human iPS cells. Hepatology. 51(1):329-35.
5. Hay DC, et al. (2008) Highly Efficient Differentiation of hESCs to Functional Hepatic Endoderm Requires ActivinA and Wnt3a Signalling. Proceedings of the National Academy of Sciences. 105 (34):12301-12306.
6. Hay DC, et al. (2008) Efficient Differentiation of Hepatocytes from Human Embryonic Stem Cells Exhibiting Markers Recapitulating Liver Development In Vivo. Stem Cells. 26 (4):894-902.