This manuscript reports the application of the selective-withdrawal coating technique to the microencapsulation of insulin-producing pancreatic islets within thin poly(ethylene glycol) coatings. These polymer coatings permit the islets to respond to changes in glucose concentration by producing insulin with a dose-response profile that is substantially similar to that of unencapsulated islets. Furthermore, the hydrogel capsules exclude the large molecules of the immune system. These results suggest that the microencapsulation technique-which combines droplet formation from a flow of two immiscible fluids with polymerization chemistries-has the characteristics required for the transplantation of islets for the treatment of Type I diabetes.

As of October 1, 2007, 25 North American medical institutions and one European islet transplant center reported detailed information to the Registry on 315 allograft recipients, of which 285 were islet alone (IA) and 30 were islet after kidney (IAK). Of the 114 IA recipients expected at 4 years after their last infusion, 12% were insulin independent, 16% were insulin dependent with detectable C-peptide, 40% had no detectable C-peptide, and 32% had missing C-peptide data or were lost to follow-up. Of the IA recipients, 72% achieved insulin independence at least once over 3 years and multiple infusions. Factors associated with achievement of insulin independence included islet size >1.0 expressed as IEQs per islet number [hazard ratio (HR) = 1.5, p = 0.06], additional infusions given (HR = 1.5, p = 0.01), lower pretransplant HbA(1c) (HR = 1.2 each %-age unit, p = 0.02), donor given insulin (HR = 2, p = 0.003), daclizumab given at any infusion (HR = 1.9, p = 0.06), and shorter cold storage time (HR = 1.04, p = 0.03), mutually adjusted in a multivariate model. Severe hypoglycemia prevalence was reduced from 78-83% preinfusion to less than 5% throughout the first year post-last infusion, and to 18% adjusted for missing data at 3 years post-last infusion. In Year 1 post-first infusion for IA recipients, 53% experienced a Grade 3-5 or serious adverse event (AE) and 35% experienced a severe AE related to either an infusion procedure or immunosuppression. In Year 1 post-first infusion, 33% of IA subjects and 35% of IAK subjects had an AE related to the infusion procedure, while 35% of IA subjects and only 27% of IAK subjects had an AE related to the immunosuppression therapy. Five deaths were reported, of which two were classified as probably related to the infusion procedure or immunosuppression, and 10 cases of neoplasm, of which two were classified as probably related to the procedure or immunosuppression. Islet transplantation continues to show short-term benefits of insulin independence, normal or near normal HbA(1C) levels, and sustained marked decrease in hypoglycemic episodes.

After the publication of this article, the corresponding authors discovered that the results of Figure 6 could not be reproduced. Upon bringing this matter to the attention of the University of Chicago Academic Fraud Committee, the Committee came to the conclusion that Matthew Connors fabricated these data. The Committee determined that there was no evidence that the rest of the authors engaged in unethical behavior or were aware of the data being fabricated. No questions were raised with respect to the results describing the design of the apparatus for the selective withdrawal method and the photochemical cross-linking of a polymeric shell around the islets. The corresponding authors and the rest of the authors (other than Matthew Connors) have requested and agreed to this retraction.

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