Islet Viability and Function

The permeability of immunoisolation devices must balance two potentially conflicting requirements. First, cells enclosed within the device must receive all the molecules and factors necessary for viability and normal function. Secondly, the destructive components of the immune system should be prevented from entering the immunoisolation device. Lymphocytes and macrophages are easily excluded by all immunoisolation devices; however, many soluble products of the immune system such as complement protein, cytokines and nitric oxide may also be cytotoxic to immunoisolated cells. Islets of Langerhans in vivo are highly vascularized by a network of capillaries that deliver nutrients and oxygen to each beta cell. However, in the immunoisolation state, vascular assess to the islet is eliminated, and solutes move to and from the islet cells by diffusion from the surrounding environment. The diffusion gradients of wastes, nutrients, and especially oxygen are important.

The oxygen levels to which the islet cells are exposed are important from two standpoints, viability and function. Because oxygen is consumed at a high rate by islet cells, particularly when stimulated by increased glucose concentration, steep gradients in oxygen concentration can develop. Thus, the oxygen concentration decreases from that of the local blood supply as it diffuses across the tissue, the immunoisolation membrane, and throughout the islet. Consequently, islet cells may be exposed to hypoxic, or even anoxic, conditions.60 This can lead to loss of cell viability and to a reduction in the insulin secretion capacity. Further studies should focus on finding a practically applicable method to reduce the barrier between encapsulated islets and the bloodstream in order to improve both the functional performance and the survival of encapsulated islet grafts. However, an interchange between vascularization and hence nutrient supply and retrievability will always be present.

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