Safety and Viability of Microencapsulated Human Islets Transplanted Into Diabetic Humans

OBJECTIVE — Transplantation of insulin-producing cells placed inside microcapsules is being trialled to overcome the need for immunosuppressive therapy. RESEARCH DESIGN AND METHODS — Four type 1 diabetic patients with no de-tectable C-peptide received an intraperitoneal infusion of islets inside microcapsules of barium alginate (mean 178,200 islet equivalents on each of eight occasions). RESULTS — C-peptide was detected on day 1 post-transplantation, and blood glucose levels and insulin requirements decreased. C-peptide was undetectable by 1–4 weeks. In a multi-islet recipient, C-peptide was detected at 6 weeks after the third infusion and remains detectable at 2.5 years. Neither insulin requirements nor glycemic control was affected. Capsules recovered at 16 months were surrounded by fibrous tissue and contained necrotic islets. No major side effects or infection occurred. CONCLUSIONS — While allografting of encapsulated human islets is safe, efficacy of the cells needs to improve for the therapy to make an impact on the clinical scene. Diabetes Care 32:1887–1889, 2009 T ransplantation of insulin-producingcells placed inside capsules is a strat-egy that is being trialled to overcome the need for immunosuppressive ther-apy in insulin-dependent diabetic peo-ple (1). We have made microcapsules of barium alginate and shown that insulin-producing porcine cells can function as efficiently inside such capsules as when nonencapsulated (2). Moreover, human islets placed in these capsules normalize blood glucose levels when engrafted in diabetic mice (3,4). In the current study, we transplanted four type 1 dia-betic humans with encapsulated human islets. RESEARCH DESIGN AND METHODS — Cadaver pancreata were obtained with consent, and islets were iso-lated by digestion with collagenase NB1 premium grade and neutral protease NB (Serva, Germany). Islets were placed in barium alginate microcapsules (2), and their median average diameter from eight islet preparations was 340 m (range 255–750). Median viability of the encapsulated islets, assessed with the fluorescent dyes carboxyfluorescein diacetate and pro-pidium iodide (2), was 73 % (range 60