review of literature on clinical pancreatology - The Pancreapedia

HISTOPATHOLOGYIn type 1 autoimmune diabetes there is a selective destruction <strong>of</strong> insulin-secreting beta cells.Around the time <strong>of</strong> clinical presentation, insulitis, a chronic inflammatory infiltrate <strong>of</strong> the isletsaffecting primarily insulin containing islets, is present in the majority <strong>of</strong> cases. Theinflammatory infiltrate consists primarily <strong>of</strong> T lymphocytes; CD8 cells outnumber CD4 cells,there are fewer B lymphocytes and macrophages are relatively scarce. beta cell death mayinvolve the Fas apoptotic pathway since they have been shown to express Fas, infiltrating Tlymphocytes express Fas-L and apoptotic beta cells have been described. Hyperexpression<strong>of</strong> class I MHC by all the endocrine cells in many insulin-containing islets is a well recognizedphenomenon, characteristic <strong>of</strong> the disease. It has been argued that this is an earlier eventthan insulitis within a given islet and appears to be due to secretion <strong>of</strong> interferon alpha bybeta cells within that islet. A recent study has found evidence <strong>of</strong> Coxsackie virus infection inbeta cells in three out <strong>of</strong> six pancreases <strong>of</strong> patients with recent-onset type 1 diabetes.Coxsackie viruses are known to induce interferon alpha secretion by beta cells and this couldinitiate the sequence <strong>of</strong> events that culminates in their autoimmune destruktion [142].Transplanting pancreatic isletsThe isolation <strong>of</strong> islets from the human pancreas critically depends on an efficient enzymeblend. Previous studies have solely focused on the presence <strong>of</strong> collagenase and neutralprotease/thermolysin. Despite improved characterization <strong>of</strong> these components, the lot-relatedvariability in efficacy still persists suggesting that additional so far disregarded enzymes arerequired for efficient islet cleavage. Varying activities <strong>of</strong> a tryptic-like enzyme were nowidentified within collagenase NB1 lots, which were selected according to a matched ratiobetween tryptic-like and collagenase activity (TLA-ratio). Rat and human pancreata wereprocessed with current standard procedures. Increasing the TLA-ratio from 1.3 to 10 percentreduced pancreas dissociation time in rats by 50 percent without affecting islet yield, viability,or posttransplant function in diabetic nude mice. Enhancing the TLA-ratio from 1.3 to 12.6percent for human pancreas processing resulted in a significant reduction <strong>of</strong> recirculationtime and increased incrementally human islet yield without affecting purity, in vitro function orrecovery after culture. Optimized pancreas digestion correlated with a higher percentage <strong>of</strong>islet preparations fulfilling quality criteria for clinical transplantation. It was concluded thatTLA is an effective component that should be included in moderate amounts in enzymeblends for human islet isolation to optimize the efficiency and minimize the lot-relatedvariability [143].Previously, it was found that human islets experimentally transplanted beneath the kidneycapsule have lower vascular density than native islets. One study aimed to investigatewhether human islets experimentally transplanted into the liver are also poorly revascularizedin the same manner as islets at the renal subcapsular site. Human islets were transplanted tonude mice. The vascular density in the intraportally transplanted human islets was found tobe similarly low as in human islets transplanted beneath the kidney capsule. The intrahepatichuman islets were coated with numerous vessels, but few vessels could be seen within theislets. Human islets transplanted intraportally into the liver become poorly revascularized.This could contribute to the loss <strong>of</strong> function in human islets transplanted into the liver overtime [144].