Successful long-term survival of pancreatic islet allografts in spontaneous or pancreatectomy-induced diabetes in dogs: cyclosporine-induced immune unresponsiveness

• Published in: Diabetes (New York, N.Y.) Vol. 34; no. 8; pp. 825 - 828
• Main Authors: ALEJANDRO, R, CUTFIELD, R, SHIENVOLD, F. L, LATIF, Z, MINTZ, D. H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.1985
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; Cyclosporins - blood; Cyclosporins - therapeutic use; Diabetes Mellitus - therapy; Diabetes Mellitus - veterinary; Diabetes Mellitus, Experimental - therapy; Diabetes. Impaired glucose tolerance; Dog Diseases - therapy; Dogs; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Graft Survival - drug effects; Islets of Langerhans Transplantation; Medical sciences; Pancreatectomy; Time Factors; Endocrinopathy; Fissipedia; Carnivora; Vertebrata; Mammalia; Pancreatectomy; Insulin dependent diabetes; Langerhansian islet; Transplantation; Dog; Survival; Allogeneic system
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.34.8.825

Nineteen pancreatectomized beagles and three spontaneously diabetic dogs were recipients of canine islet allografts from one or more unrelated donors. The islets, enriched 30-45-fold for endocrine cells and contained in a packed cell volume of less than 1.5 ml, were engrafted in the livers of recipient animals. Treatment of diabetic recipients with cyclosporine (CsA) was begun 3-5 days before islet transplantation and the initial dosage was adjusted to attain and maintain CsA serum trough levels between 400 and 600 ng/ml. Five dogs with CsA levels less than this (155 +/- 35 SEM ng/ml) at the time of transplantation promptly rejected their grafts, whereas rejection was encountered in only 1 of 17 diabetic animals in which the initial level exceeded 400 ng/ml. CsA was discontinued 30, 60, or 90 days after continuous therapy in 10 animals. Graft failure was observed 2 mo after stopping CsA in 1 animal and 5 mo in the other. Eight other islet allograft recipients have sustained fasting euglycemia for 7 and 8 mo in 2 and for at least 2 mo in the remainder. These results demonstrate that short-term CsA therapy prolongs survival of islet allografts and induces a state of immune unresponsiveness to islet alloantigens in dogs with experimental and spontaneous diabetes. The findings are unique for a nonrodent mammal and thus hold promise that similar results may be achieved for islet allografts of other mammalian species, including humans.