Sub-Theme: Pancreas and Islet Cell Transplantation

Oxford has one of the world’s most active integrated beta-cell replacement programmes, with more than 800 whole pancreas transplants performed over the past 12 years, and islet isolation and islet transplant programmes amongst the most established in Europe. Both clinical services are nationally commissioned and attract patients from around the country, and the Oxford team play a central role in UK service development. The ‘state of the art’ DRWF Human Islet Isolation is one of only a handful in Europe and has been awarded the status of being a JDRF Islet Resource Centre.

All these strengths make Oxford uniquely placed to provide a world-leading translational NIHR research platform to evaluate and develop beta-cell replacement therapies, with the ultimate aim of translating islet replacement to children.

Our sub-theme incorporates a broad range of clinicians and scientists involved in the fields of transplantation, diabetology, nephrology, and paediatrics. It collaborates closely with other BRC Diabetes and Metabolism sub-themes and with the BRC Imaging and Surgical Innovation and Evaluation Themes.

Specific translational research projects within our subtheme include:

• Testing of a unique Oxford-developed vascularised donor-specific skin graft, to provide early warning of rejection and allow patient self-monitoring. Using longitudinal data we will develop a transplant HOMA calculator.
• Developing technologies, including macro-encapsulation of islets, to provide protection from allo-immune responses and post-transplant inflammatory and test new scaffolds, including vascularised myocutaneous grafts containing islets engrafted during ex vivo perfusion
• Conducting a formal health-economic analysis of the effect of both simultaneous pancreas-kidney and islet transplantation
• Investigating the proteomic profiles of pancreatic digest from different donor pancreases during human islet isolation and correlate this with islet isolation outcomes and post-transplant graft function. This will lead to novel strategies for optimising pancreas and islet preservation
• Testing GLP-1 treatment and other novel interventions designed to enhance graft function and lifespan. Having previously identified unique genetic markers that predict outcome, we will further develop donor and recipient genetic profiling to improve patient selection, risk stratification, organ utilisation and outcomes
• Following our successful pilot study of cardiac MR in pancreas transplant patients, showing significant structural abnormalities on SMolli T1-mapping, longitudinal studies will determine the natural history of cardiac changes and the effect of transplantation

Sub-Theme Leaders: Peter Friend and Paul Johnson

Key Researchers: Patrik Rorsman, Fredrik Karpe