Public Funding for Definigen Limited

Development of an optimised pancreatic cell tool kit to enable accelerated diabetes drug discovery. Diabetes drug discovery is constrained by the lack of availability of human pancreatic islets and their donor-dependent variability. We will develop pancreatic beta cell models for type 2 diabetes research from human induced pluripotent stem cells (hiPSCs), improving their maturity and function. Complementary CRISPR gene-edited disease models will also be generated. 3D cell culture systems will then be developed using automation compatible 96- or 384-multiwell plate formats for high throughput screening and downstream drug evaluation. Market readiness of this platform will be evaluated by an industry beta testers.

The aim of this project is to provide cell tools to help scientific researchers working on a common liver disease called non-alcoholic fatty liver disease (NAFLD). The cell products are human liver cells with genetic mutations inserted that ultimately disrupt the function of the cells duplicating NAFLD in the cells, which can be grown in a lab in large quantities. This "disease in a dish" approach can contribute to the greater understanding of the causes on NAFLD. This disease is particularly important as it is estimated that 25% of the UK population has the condition which if not effectively treated and managed can progress to severe life-threatening liver disease. The cell models can be used to test large numbers of potential drugs to identify the best drug candidates which could be further developed and provide safe and effective drug therapies that can help patients.

NASH presents a significant unmet medical need in more economically developed nations, affecting up to 5% of the US population alone. There is currently no medical treatment for NASH, where the condition is a precursor to cirrhosis and hepatocellular carcinoma, conditions with very poor prognoses. One key limiting factor in the development of a treatment for NASH is a lack of suitable in vitro models. The project will produce a highly representative, medium throughput, 3D perfused model of NASH using both primary human and induced pluripotent stem cell derived hepatocytes, kupffer and stellate co-cultures. These models can be used in collaboration with industry to enable highly effective drug discovery studies and macrosteatotically relevant ADME/Toxicology studies.

Diabetes is a serious condition where the amount of sugar (glucose) in the blood is too high because the body either cannot produce enough of the hormone insulin or cannot use the insulin effectively. There is no known cure for diabetes, and although many treatment options are available, they often do not prevent the disabling long-term complications of the disease. In the search for new treatments, researchers are now trying to find drugs that will protect the insulin-producing (beta) cells of the pancreas. To support this research, the aim of this project is to develop a new 3D human cell-based model of pancreatic beta cell health. The model will be developed using freshly isolated human islets. The team will then investigate whether a more sustainable human cell source can be used and whether the model can be miniaturised, so more drugs can be tested in each assay. If the project is successful, it will enable the faster testing of potential new anti-diabetes drugs, and ultimately help to identify new and improved treatments for diabetes. If widely adopted, the resulting model will also reduce the number of animals currently used in diabetes research and drug discovery.