Silicone rubber membrane devices permit islet culture at high density without adverse effects.

Introduction: Conventional culture conditions, such as in T-flasks, require that oxygen diffuse through the medium to reach the islets; in turn, islet surface area density is limited by oxygen availability. To culture a typical clinical islet preparation may require more than 20 T-175 flasks at the standard surface area density of 200 IE/cm. To circumvent this logistical constraint, we tested islets cultured on top of silicon gas-permeable (GP) membranes which place islets in close proximity to ambient oxygen.

Hypoxia within subcutaneously implanted macroencapsulation devices limits the viability and functionality of densely loaded islets.

Introduction: Subcutaneous macroencapsulation devices circumvent disadvantages of intraportal islet therapy. However, a curative dose of islets within reasonably sized devices requires dense cell packing. We measured internal PO2 of implanted devices, mathematically modeled oxygen availability within devices and tested the predictions with implanted devices containing densely packed human islets.

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

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 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 was used to assess the part of islets that contributed to insulin secretion.

Oxygenation of the Intraportally Transplanted Pancreatic Islet.

Intraportal islet transplantation (IT) is not widely utilized as a treatment for type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been studied extensively. We present a diffusion-reaction model that predicts the presence of an core and a larger core within intraportally transplanted islets.

Effect of oxygen supply on the size of implantable islet-containing encapsulation devices.

Beta-cell replacement therapy is a promising approach for the treatment of diabetes but is currently limited by the human islet availability and by the need for systemic immunosuppression. Tissue engineering approaches that will enable the utilization of islets or β-cells from alternative sources (such as porcine islets or human stem cell derived beta cells) and minimize or eliminate the need for immunosuppression have the potential to address these critical limitations. However, tissue engineering approaches are critically hindered by the device size (similar to the size of a large flat screen television) required for efficacy in humans.