Transplantation sites for porcine islets.

AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen. This was demonstrated by IVGTTs showing significant difference between the peak glucose levels: 22.8 ± 2.9 mmol/l for kidney compared with 26.8 ± 1.3 mmol/l for spleen and 24.7 ± 1.7 mmol/l for liver. CONCLUSIONS/INTERPRETATION: Kidney grafts are not as feasible in humans and liver results were relatively poorer than spleen. For islet transplantation to be viable and successful in the longer term, there remains a need for future investigation of alternative sites.

Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes.

UNLABELLED: BACKGROUND: Development of a limitless source of ß cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet-kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre-clinical animal model as a means to establish whether this would be feasible before moving to the clinic. METHODS: Inbred 'Westran' pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. RESULTS: Under the kidney capsule of the first transplant group (n = 6), the FPPF-transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal-grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet-like structures up to and beyond 224 days after the original transplantation under the kidney capsule. CONCLUSIONS: This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single-transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.

Subcapsular fetal pig pancreas fragment transplantation provides normal blood glucose control in a preclinical model of diabetes.

OBJECTIVE: Identifying a limitless source of ß-cells that survive transplantation into a neovascularised site and provide normal blood glucose control remains an important goal in the development of pancreatic islet xenotransplantation. It was our hypothesis that fetal porcine pancreas fragments could achieve these objectives, and this was tested in a large preclinical animal model. RESEARCH DESIGN AND METHODS: Inbred "Westran Pig" fetal porcine pancreas fragments were transplanted beneath the splenic capsule into syngeneic Westran Pig recipients without immunosuppression, and 3 months later, a total native pancreatectomy was performed to demonstrate function. RESULTS: Histologic analysis showed appropriate development of islet-like structures up to and beyond 120 days after transplantation. After native pancreatectomy, recipients survived more than 100 days without exogenous insulin and with normal glucose homeostasis as assessed by normal glucose tolerance tests, K values, and normal glucagon secretion. CONCLUSIONS: This study confirms that fetal pig islet tissue has the potential to mature and function normally in a neovascularised site, hence, avoiding the innate immune destruction that occurs when islet tissue is exposed directly to the circulation.