Objective
The main objective of the proposal is to supply 1 million (IEq) islets per annum for research. These human islets will come from both normal donors, and those with diabetes. We also aim to provide researchers with pancreatic tissue biopsies/slices to support their research, both from normal donors, and those with diabetes.
Background Rationale
Previously, basic research on pancreatic islet function and treatment of diabetes has been carried out primarily with animal models. In order to understand the pathogenesis of diabetes better and to devise better ways to treat the disease, a wider understanding of human pancreatic islet function is necessary. The provision of human islets and tissue from normal donors and those with diabetes will facilitate this process. Importantly, the inclusion of pancreatic tissue into our provision model will allow researchers to study islets in situ, within their native pancreatic environment. Indeed, some of our collaborators currently use tissue slices to investigate the dysregulation of glucagon secreting alpha cells and somatostatin secreting delta cells in Type 1 diabetes. Determining the mechanism behind the abnormal function of these cells will result in novel diabetes treatments, which specifically target these cell types. Regular supply of pancreatic tissue from a wide range of donor types is essential for this project, and many others, to be able to continue.
Description of Project
Human pancreatic tissue and human islets of Langerhans (islets) are a vital resource for researchers investigating the causes of Type 1 diabetes and those trying to develop novel treatments. Over the past 12 years, our Oxford Islet Isolation Facility has established ourselves as the JDRF UK Human Islet Resource Center. This is a comprehensive collaboration to provide human islets and pancreatic tissue to different researchers across the UK and in mainland Europe. Islet isolations are performed within our ‘state of the art’ isolation facility, from pancreases that have been allocated for research. In addition to routinely receiving pancreases from normal donors, we now have the exciting opportunity to receive pancreases from donors with diabetes, as part of the novel INOAR (Increasing the Number of Organs Available for Research) and QUOD (Quality in Organ Donation) initiatives. Furthermore, islets can on occasion become available for research as result of clinical isolations that have failed to meet the strict product release criteria in terms of yield, purity, viability (and where appropriate research consent has been granted by next of kin). Our facility will then co-ordinate the distribution of these clinical islets to our research end-users. The aim of the application is to continue to supply the network of research labs we have previously established with islets and tissue from both normal donors and those with diabetes; this will enable the research groups to continue their studies using human islets and tissue.
Anticipated Outcome
We will be able to continue to supply high quality normal and diabetic human islets and pancreatic tissue to research laboratories that require them for their studies. This will result in a continued output from these research laboratories and the subsequent publication of their work in peer reviewed journals and presentations at scientific meetings.
Relevance to T1D
The human islets we have distributed have been used to investigate numerous aspects of the mechanism of insulin secretion and the pathogenesis of diabetes. Directly relevant to Type 1 diabetes are projects investigating the role of human beta cell proteins in stimulating the activity of the patient’s immune system and effects of disease related chemical signals on human islet function, human islet tissue as a source of pluripotent stem cells for Beta cell replacement therapy, organ regeneration studies and the creation of a bio-artificial pancreas to treat Type 1 diabetes. Most importantly, our new novel platform for accessing human islets and pancreatic tissue from donors with diabetes through the joint INOAR and QUOD initiatives will enable direct investigation into the pathogenesis of diabetes.