Histomorphological characteristics of the porcine pancreas as a basis for the isolation of islets of Langerhans

Abstract: Isolation of porcine islets of Langerhans for future clinical xenotransplantation in type I diabetic patients is limited by the difficulty to isolate sufficiently functioning islets and by their particular fragility. Seven domestic pig races and the wild boar were investigated histologically to obtain detailed information on islet profiles, numbers, sizes, and volume density of the endocrine tissue. Theoretically calculated islet numbers were correlated with those obtained after islet isolation. Results: 1) Porcine islets are round, oval, dumbbell-like and triangular, and, as expected, occur in all intermediate profiles. Round and oval islets predominate. These profiles are also detected in crude islet preparations, which indicates that they can withstand the enzymatic digestion process. 2) The total number of islets varies greatly in all eight pig races, with, e.g., the wild boar showing twice as many islets (approx. 500/cm² tissue section) as the minipig (approx. 250/ cm²). 3) The tail of the pancreas, which is usually used for islet isolation, accounts for about 50% of the pancreas mass. 4) The majority of islets, 64.3% (range 59.8–68.9%), of the seven domestic races are 50–100 μm in diameter. With its 86% the wild boar is a remarkable exception. German landrace pigs show the greatest number (2%) of large islets (250 to >300 μm. 5) With 3.4%, German landrace pigs reveal the greatest islet volume density of all pig races (range 2.6–4.2%). 6) Only 25% of all islets are surrounded by a collagen “capsule” that covers >75% of the islet surface. Roughly 33% of all islets are “capsulated” by collagen type I, III, and IV fibers to an extent of <25%. 7) In young pure bred pigs (7–12 month old) only 3.0–10.6% of all theoretically available islets can be isolated during the enzymatic digestion. However, much better islet yields (30.1%) can be obtained from adult hybrid pigs (3 years old) much better islet yields (30.1%) can be obtained than from young hybrid pigs (7.6%). It may be concluded from our results that histological parameters-besides those already known (pH of the isolation medium, trypsin inhibition by Pefabloc-may have a greater influence on porcine pancreatic islet isolation than was assumed so far.