TRANSPLANTATION OF PURIFIED FROZEN/THAWED CANINE PANCREATIC ISLET ALLOGRAFTS WITH CYCLOSPORINE

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Abstract
We studied the survival of defined volumes of highly purified frozen/thawed islets transplanted into the spleen of 4 groups of apancreatic mongrel dogs (total, 21), with or without cyclosporine from day −4 to day 30: group 1 (controls), without CsA, autograft of mean (± SE) islet volume 5±1 μl/kg body weight; group 2, single-donor allograft, and group 3, multiple-donor allograft (both, 6±1 μl/kg), both with CsA; and group 4, large-volume multiple-donor allograft (24±1 μl/kg) with CsA. Grafts were cooled slowly to −40°C, stored at −196°C, and thawed rapidly. The CsA dose was adjusted to maintain whole-blood trough values of 600–800 μg/L, and allograft recipients manifesting early hyperglycemia were given insulin to maintain plasma glucose concentration below 150 μg/dl. In group 1, two dogs died early (graft failure in 1, intussusception in 1), but the remaining five were normoglycemic at 30 days. In groups 2 and 3, hyperglycemia ensued from about day 2.5, but 4 of 5 grafts in group 2 and all grafts in group 3 secreted insulin into the splenic vein at 30 days. In group 4, normoglycemia ensued within 24 hr of transplantation and was maintained in all 6 dogs for 30 days; the grafts failed 15±2 days after CsA was stopped. The data demonstrate prolonged function of purified frozen/thawed islets after transplantation into these outbred dogs but indicate a need for a greater volume of allogeneic islets from multiple donors than of autologous islets to achieve normoglycemia.

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