Induction and Amelioration of Environmental Stress in Isolated Islets Until Transplantation

Pancreatic tissue, processed for subsequent clinical islet transplantation, is exposed to enormous biophysical and biochemical stress causing injury and death in a large number of islets even before they are transplanted. Since several steps within this heterogenous process are associated with non-physiologic and harmful ambient conditions the damaging mechanisms are attributed to four different determinants: 1) brain death in the organ donor, 2) insufficient oxygen supply during pancreas procurement, isolation processing, culture and after intraportal transplantation, 3) destruction of the natural environment during isolation, and 4) exposure to toxic reagents during the isolation process. Potential strategies to ameliorate the detrimental impact of these factors on the quality of subsequently transplanted islets are discussed.