Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine A, mycophenolate mofetil, and leflunomide remain normo glycemic for up to 100 days

Background, Transplantation of adult porcine islets (APIs) offers a possibl e means of treating diabetes. However, isolating APIs has been notoriously difficult. Furthermore, islet xenograft rejection must be prevented. Materials and Methods. APIs were isolated by a modified automated method. A PI quality was assessed by static glucose stimulation (SGS), by transplanta tion to diabetic nude mice and by intraperitoneal glucose tolerance tests ( IPGTTs), The morphologic characteristics of API xenograft rejection in rats were studied immunohistochemically. Furthermore, APIs were transplanted to diabetic rats that were either left untreated or immunosuppressed with cyc losporine A (CsA), mycophenolate mofetil (MMF) and leflunomide (LEF). B-glu cose and porcine C-peptide levels were monitored and grafts were studied mo rphologically. Results. Large numbers of APIs were isolated. At SGS, insulin release incre ased significantly. Ah nude mice transplanted with APIs were normoglycemic within 24 hr and remained so for up to 1 year. During IPGTTs, B-glucose lev els were rapidly regulated to porcine levels. In untreated rats, API xenogr afts were destroyed within 6 days by a cellular infiltrate consisting mainl y of macrophages, In untreated diabetic rats normoglycemia was sustained fo r 5.5 +/-0.3 days, Rats immunosuppressed with CsA+MMF+LEF remained normogly cemic for 59.6 +/- 11.3 days. In 3 of 11 rats, normoglycemia was sustained for up to 101 days. Porcine C-peptide was detected in serum. At recurrence of hyperglycemia, many mononuclear cells were found close to the xenografts . However, only occasional cells infiltrated the grafts and many APIs were intact. Conclusions. Well-functioning APIs can be isolated in large numbers. API xe nografts can be protected from rejection and can maintain an adequate funct ion for up to 100 days, in rats immunosuppressed with CsA+MMF+LEF.