Transplantation of pancreatic islets contained in minimal volume microcapsules in diabetic high mammalians

To minimize technical problems relating to excessive size (600-800 mu in diameter) of standard alginate microcapsules (CSM) for pancreatic islet graft immunoisolation, we have developed two novel minimal volume, chemically Identical, capsule prototypes (MVC): 1) coherent microcapsules (Chl), and 2) medium-size microcapsules (300-400 mu, MSM). Chi, which envelop each individual islet within a thin alginate hydrogel cast, are prepared by emulsification, whereas MSM are made by atomizing the islet-alginate suspension through a special microdroplet generator. Upon graft into diabetic rodents, Chi have shown to immunoprotect both allo- and xenogeneic nondiscordant islets, and restored normoglycemia, In higher mammals, at subtherapeutic doses, CM fully immunoprotected islet allografts (pig-->pig), but only temporarily xenografts (dog-->pig). We then used MSM to immunoisolate canine islet allografts in the peritoneal cavity of dogs with spontaneous insulin-dependent diabetes, Of three grafted dogs, two showed full remission of hyperglycemia with insulin withdrawal. MSM could represent an intermediate solution between CSM and CM for peritoneal immunoisolated islet transplants.