In Vitro Assessment of Human Islet Vulnerability to Instant Blood-Mediated Inflammatory Reaction (IBMIR) and Its Use to Demonstrate a Beneficial Effect of Tissue Culture.

Culture of human pancreatic islets is now routinely carried out prior to clinical islet allotransplantation, using conditions that have been developed empirically. One of the major causes of early islet destruction after transplantation is the process termed instant blood-mediated inflammatory reaction (IBMIR). The aim of this study was to develop in vitro methods to investigate IBMIR and apply them to the culture conditions used routinely in our human islet isolation laboratory.

Collagenase does not persist in human islets following isolation.

Optimal human islet isolation requires the delivery of bacterial collagenase to the pancreatic islet-exocrine interface. However, we have previously demonstrated the presence of collagenase within human islets immediately following intraductal collagenase administration. This potentially has significant implications for patient safety.

Collagenase penetrates human pancreatic islets following standard intraductal administration.

Background: : To optimize human islet isolation, it is important to improve our understanding of the collagenase digestion phase. Previous studies of collagenase action were mostly concerned with optimizing its composition, but the delivery and distribution of collagenase at the islet-exocrine interface is likely to be important for liberation of intact islets. The aim of this study was to characterize collagenase distribution in relation to islets in infused human pancreases.

Characterisation of collagen VI within the islet-exocrine interface of the human pancreas: implications for clinical islet isolation?

Background: To optimize the methods used for human islet isolation for transplantation, it is important to improve our understanding of the structure of the islet-exocrine interface. In this study, the composition of collagen subtypes in the interface have been characterized and quantified in human pancreas.

Methods: Human adult pancreases were retrieved from older (mean age 55.

Adverse outcome of human islet-allogeneic blood interaction.

Background: A report of inflammatory damage when islets come into contact with allogeneic blood prompted us to confirm the finding.

Methods: Fresh handpicked human islets were incubated in blood group matched, nonsensitized allogeneic blood. Destruction was quantified by assaying the supernatants for proinsulin release and by blood clot histology.

The interaction between primate blood and mouse islets induces accelerated clotting with islet destruction.

Background: Mouse islets transplanted under the renal subcapsular space of cynomolgus monkeys are subject to a form of hyperacute rejection, the mechanism of which is unclear. As islets are in contact with whole blood at the time of transplantation, the effect of platelets and the coagulation cascade on islet destruction was assessed.

Methods: Coagulation was assessed using thromboelastography on citrated/recalcified human blood samples with freshly isolated C57/Bl6 mouse islets.

Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunction.

Background: Chronic renal allograft failure (CAF) is influenced by both allo-dependent and independent factors and is a major cause of graft loss in clinical renal transplantation. We evaluated a novel membrane-bound free radical scavenger, lecithinized superoxide dismutase (lec-SOD), to determine its potential in limiting the harmful effects of ischemia/reperfusion injury on CAF.

Methods: Fisher rat kidneys were stored for either 1 hour or 18 hours in cold Marshall's preservation solution either with or without lec-SOD and transplanted into Lewis recipients.