The development of 3-dimensional implantable liver organoids
Liver disease is the 5th commonest cause of death in the UK. 16,087 people in the UK died from liver disease in 2008, a 4.5% increase since 2007 and trends are rising.
The only curative option for end-stage cirrhosis and fulminant liver disease, that meets “Kings College Criteria”, is liver transplantation. However, organ availability cannot meet demand and many patients die waiting for an organ. Those who do receive transplantation require lifelong immunosuppression with increased risks of infection, cancer, renal and cardiovascular disease.
There is a clear imperative to provide alternatives to liver transplantation. Recent studies have shown human pluripotent stem cells (hPSC) can form primitive liver organoids (Takebe et al. Nature 2013). While providing proof of concept, the in vitro derived spheroids are tiny and lack a functional biliary system, requiring transformative innovation before they can be used clinically.
To deliver this we have assembled a team with complementary expertise in the production and use of stem cell derived hepatocyte and cholangiocytes-like cells, hepatocyte niche construction, and three-dimensional scaffold production and in vivo modelling.
This collaborative group includes scientists and clinicians with experience in human cell production, GMP cell production and clinical cell therapy for liver disease. This group is ideally placed to translate these pre-clinical observations into a therapy for patients with liver failure or metabolic liver diseases, and particularly the use of liver buds derived from genetically corrected iPS cells in the case of liver disease caused by single gene defects.
CRM researcher Dr David Hay is leading the project.