Transplantation of purified frozen/thawed canine pancreatic islet allografts with cyclosporine.
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 microliters/kg body weight; group 2, single-donor allograft, and group 3, multiple-donor allograft (both, 6 +/- 1 microliters/kg), both with CsA; and group 4, large-volume multiple-donor allograft (24 +/- 1 microliters/kg) with CsA. Grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. The CsA dose was adjusted to maintain whole-blood trough values of 600-800 micrograms/L, and allograft recipients manifesting early hyperglycemia were given insulin to maintain plasma glucose concentration below 150 mg/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.
Cattral
M S
MS
Department of Surgery, University of Alberta, Edmonton, Canada.
Warnock
G L
GL
Evans
M G
MG
Rajotte
R V
RV
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015925:Cryopreservation; D003524:Cyclosporins / Q000097:blood / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D006085:Graft Survival; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation; D008297:Male; D014184:Transplantation, Homologous
D001786:Blood Glucose; D003524:Cyclosporins; D007328:Insulin