(76a) Overcoming Oxygen Supply Limitations in Islet Transplantation

Islet transplantation is an approved treatment for diabetes in much of the world but not yet in the USA. Recipients must be immunosuppressed, which has motivated extensive study of islet micro- and macro-encapsulation approaches. Encapsulated islets are separated from the bloodstream and receive oxygen by diffusion from the nearest source, and oxygen supply limitations can have deleterious effects on islet viability and function. More than 30 years ago, Martin Yarmush suggested these issues needed investigation because islets in the pancreas are exposed to high blood perfusion rates with arterial blood having pO2 in excess of 100 mmHg. Studies revealed that insulin secretion rate was increasingly comprised as pO2 decreased to low values that nevertheless were substantially higher than required for maintenance of viability. Ensuing studies have endeavored to quantify the effects of oxygen supply limitations and to develop solutions to overcome this problem. These efforts are reviewed with emphasis given to recent results with exogenous oxygen supply that give promise to maintenance of viability and function of implanted macroencapsulation devices over extended periods of time.