Cold storage preservation of islet and pancreas grafts as assessed by in vivo function after transplantation to diabetic hosts

The major goal of hypothermic (4-8 °C) preservation of intact pancreases or isolated islets will be to provide sufficient time for HLA typing, cross matching, selection, and preparation of recipients-logistical efforts requiring 12-72 hr for clinical kidney transplantation, usually <48 hours. Some investigators have studied in vitro function of islets after cold storage, but the critical test of viability-permanent restoration of normoglycemia after transplantation to diabetic recipients-has been tested in only a few experiments. Reversal of hyperglycemia by syngeneic or autogenic transplants in diabetic animals has been achieved after CS of dispersed pancreatic tissue from neonatal rats in GIB media for ≤ 146 hr, adult dogs in TCM 199 for ≤24 hr, and adult DL-ethionine-treated rats in RPMI 1640 for ≤72 hr. In the neonatal rat donor model, intravenous glucose tolerance test (IVGTT) results were similar in recipients of fresh or stored islets; in the dog model, IVGTT test results were variable, but generally inferior in recipients of stored as compared to fresh islets; in the adult rat donor model, recipients of ≤24-hr coldstorage islets had insulin and IVGTT K values similar to those of recipients of fresh islets, but the success rate progressively declined for CS times >24 hr. Various agents were added to the media, but the need or the optimal concentrations were not critically determined by using different recipes for different groups of recipients. Cold storage of intact pancreas autografts has been tested in dogs; simple electrolyte solutions are satisfactory for 24 hr, but only a silica gel-filtered plasma-based solution has been reliable for 48 hr. Pulsatile machine perfusion (PMP) of canine pancreas grafts for 24 hr has had a success rate similar to CS in some experiments and lower in others. PMP has been almost totally unreliable for >24 hr. Further refinements are needed if preservation of islets for >24 hr and pancreases for >48 hr are to be consistently successful. If current experimental techniques are effective for human islets or pancreases, however, these times are sufficient to complete the logistical maneuvers required before transplantation.