A preclinical assessment of the non-heart beating donor pancreas for islet transplantation

The results of islet transplantation have been significantly improved in recent years following major advances made by the Edmonton group in Canada. These included transplanting fresh islets from more than one donor combined with a new less diabetogenic immunosuppressive protocol. Clinical islet transplant programs will be limited by the declining numbers of organ donors. Non-heart beating donors have been used to expand the renal donor pool, however the pancreas in particularly susceptible to warm ischaemia and may therefore not be suitable for islet transplantation.;The aim of this thesis was to evaluate the use of islets from non-heart beating donors in pre-clinical animal models. Different preservation methods were used including new and old preservation solutions along with the two-layer method (TLM) to attempt rodent pancreas resuscitation. However, even a short period of warm ischaemia led to poor islet yields and viability. A proportion of this work was to examine the use of ADP:ATP ratio as a potential viability test to estimate the degree of warm ischaemic damage.;Pulsatile machine perfusion has been a promising method for kidney preservation. A Waters RM3 perfusion machine was compared to both conventional cold storage and TLM for porcine pancreas preservation. Unfortunately, islet fragmentation and poor islet yields were a problem following machine perfusion suggesting that cold storage should remain the gold standard preservation method. In conclusion, the use of the non-heart beating donor pancreas for islet transplantation still remains a problem until more effective preservation methods are developed