We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received 1 to 2 islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-α blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels, and C-peptide production) and for adverse events associated with the study protocol. Of the 6 recipients, 5 were insulin-independent at 1 year, and 4 continue to be insulin-independent at a mean of 3.4 ± 0.4 years posttransplant. None of the 6 recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ±21.2 mL/min/1.73m2 pretransplant to 82.6 ±19.1 mL/min/1.73m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in 4 of 6 recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.

We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.

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However, the eff ect of SU6656 on cell survival in ATC cells has not been evaluated. p21/WAF1 modulates survival and growth via a p53-dependent or-independent pathway [ 13 ]. p21 mediates cell cycle arrest by impediment of p53-dependent cyclin dependent kinases, while it represses cell death by hindrance of p53dependent or-independent pathway [ 13 ]. p21 is present in 40 % of patients with papillary thyroid carcinoma (PTC), 7 % of patients with poorly differentiated thyroid carcinoma, and 0 % of patients with ATC, and its levels are reduced in PTC cells which have a tendency to undergo early metastasis [ 14 , 15 ]. Even though changes in p21 caused by some agents are related to survival of human cancer cells, the relationship of p21 with cell survival in SU6656-treated ATC cells has not been clarifi ed [ 16-18 ]. PI3K/Akt signaling is involved in the control of multiple cellular processes including survival, growth, proliferation, diff erentiation, and migration [ 19 ] .

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