- Mr Paul Johnson, Principal Investigator
- Dr Stephen Hughes, Co-Investigator
- University of Oxford, Oxford, UK
- Optimisation of Human Pancreatic Islet Isolation
Islet transplantation offers a potential ‘cure’ for patients with type 1 diabetes (T1DM) and could be applied widely, subject to improvement in immune-suppression therapies. It is currently also restricted by the limited number of donor pancreases from which to isolate islets and by the inability to produce sufficient numbers of quality islets from pancreases. Islets are isolated by digestion of the pancreas with a commercially produced collagenase blend of enzymes. The currently available enzymes require mixing of a two-component system at the best ratio to achieve the optimal effect. Even the best centres are only successful in obtaining transplantable yields in approximately 50% of cases after careful donor selection. Indeed, these donors (those with a high body mass index [BMI], aged approximately 50 years) might be anticipated to yield potentially poorly functioning islets; the truly best physiological function is found in islets from younger donors from whom it is difficult to isolate sufficient numbers for transplantation.
This proposal will address the problems discussed above. We propose that islet isolation can be optimised by understanding the interaction between pancreatic substrates and the components of collagenase. We will investigate the composition of extracellular matrix proteins - the substrates - surrounding islets in different donor groups and how these components interact spatially in a 3-dimensional structure around the islets. We will determine the optimal ratios of enzyme blend components for the digestion of the specific substrates surrounding islets in pancreas specimens from donors from different groups (younger or older than 30 years, with high or low BMI) using a novel assay system. The degree of digestion will be correlated with islet isolation outcome in our (clinical) islet isolation program.