Mathematical predictions of oxygen availability in micro‐ and macro‐encapsulated human and porcine pancreatic islets

Source abstract

Abstract Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing beta‐cells. Using mathematical modeling, we investigated the influence of the pO 2 on islet insulin secretory capacity and evaluated conditions that could lead to the development of tissue anoxia, modeled for a 300 μm islet in a 500 μm microcapsule or a 500 μm planar, slab‐shaped macrocapsule. The pO 2 was used to assess the part of islets that contributed to insulin secretion. Assuming a 500 μm macrocapsule with a 300 μm islet, with oxygen consumption rate (OCR) of 100–300 nmol min −1 mg −1 DNA, islets did not develop any necrotic core. The nonfunctional zone (with no insulin secretion if pO 2 < 0.1 mmHg) was 0.3% for human islets (OCR ~100 nmol/min/mg DNA) and 35% for porcine islets (OCR ~300 nmol/min/mg DNA). The OCR of the islet preparation is profoundly affected by islet size, with optimal size of <250 μm in diameter (human) or <150 μm (porcine). Our data suggest that microcapsules afford superior oxygen delivery to encapsulated islets than macrocapsules, and optimal islet function can be achieved by encapsulating multiple, small (<150 μm) islets with OCR of ~100 nmol min −1 mg −1 DNA (human islets) or ~200 nmol min −1 mg −1 DNA (porcine islets).