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Porcine islets are being extensively investigated as alternative sources of insulin-secreting cells for transplantation in insulin-dependent diabetic patients. The present review focuses on recent advances in porcine islet transplantation with particular emphasis on new transgenic pig models, islet encapsulation, and biosafety considerations.Genetic modifications aimed to reduce islet cell immunogenicity, to prolong their survival, and to improve their secretory function have been reported. Micro- and macroencapsulation of porcine islets should allow their use in the clinic with no or minimal immunosuppression. The risk of porcine endogenous retrovirus transmission is being re-evaluated since no evidence for infection was found in several clinical and preclinical studies.Pig islet xenotransplantation is still a serious contestant in the race for novel treatments for type I diabetes. Adequate pathogen screening, animal selection, and the establishment of microbiological, genetic, and potency release quality controls should increase safety and efficacy of future porcine islets transplantation clinical trials.