Studies into the efficacy of using non-purified islets for clinical islet transplantation

Islet purification prior to allo transplantation currently forms the clinical gold standard, despite the fact that purification protocols result in significant islet losses and remove potential islet precursors and tissue that may provide islets with bio-trophic support Conversely, non-purified islet preparations retain endocrine mass and within the sphere of islet auto transplantation have been associated with excellent long-term graft function. This study comprises of an analysis of peri-operative factors and the long-term graft function of patients’ auto transplanted with either purified (n=14) or nonpurified islets (n=23). Complementary in-vitro studies were carried out to assess the effect of non-islet tissue on islet viability, integrity and function (n=8), whilst a histology-based study (n=23) assessed whether transplantation of non-islet cells, particularly islet precursors, had a long-term effect on graft function in the clinical setting. Clinically, non-purified islets did not significantly increase peri-transplant venous pressures and perioperative factors including ITU stay, blood loss and liver function were comparable in both groups. Analysis of the 5 year post-transplant period demonstrated that although insulin release in response to glucose was initially superior following transplant of purified islets, non-purified islets were associated with stable long-term function. In-vitro studies reiterated these findings, revealing that islet viability and function were comparable in both groups, however, retention of intracellular insulin was found to be superior within non-purified preparations with some evidence that ductal tissue provided islets with bio-trophic support. Histology-based analysis of patient pancreata suggested a positive role for islet precursors demonstrating significantly superior blood glucose, HbA1c and C-peptide values associated with the transplantation of ductal cells and non-islet PDX-1 and glucagon positive cells. The results of this study indicate that transplantation of non-purified islets can be performed safely and with comparable long-term graft function as purified islets. Additionally, these studies potentially suggest that ductal tissue may help to preserve islet integrity, whilst certain precursors cells found within the acinar parenchyma and ductal epithelium may improve long-term islet graft function.EThOS - Electronic Theses Online ServiceGBUnited Kingdo