Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets

There are several approaches of immunoprotection of pancreatic islets for t he purpose of successful allo- or xenotransplantation in the absence of imm unosuppressive medication. Extravasculair approaches are either mac roencap sulation (large numbers of islets together in one device) or microencapsula tion. The latter approach is to envelop each individual islet in a semiperm eable immunoprotective capsule. Quite promising results have been achieved with polylysine-alginate microencapsulated islet grafts in rodents, but cli nical application is still restricted to a very small number of cases. Rele vant considerations regard the following aspects. The biocompatibility of t he microcapsules is influenced by the chemical composition of the materials applied and by mechanical factors related to the production process. With purified instead of crude alginates, the percentage of capsules with fibrot ic overgrowth is reduced to approximately ten percent, and the remaining ov ergrowth is mainly explained by mechanical factors, i.e. inadequate encapsu lation of individual islets. Even with purified alginates, however, the dur ation of encapsulated graft function is limited to a period of six to twent y weeks. Obviously, other factors than bioincompatibility play a role, whic h factors have to be identified. The limited duration of graft survival can not be explained by rejection since, in rats, survival times of encapsulate d isografts are similar, if not identical, to those of encapsulated allogra fts. An important factor is probably insufficient nutrition as a consequenc e of insufficient blood supply of the encapsulated and thus isolated islet. This also influences the functional performance of encapsulated islet graf ts. Although normoglycemia can be readily obtained in streptozotocin diabet ic rat recipients, glucose tolerance remains severely impaired, as a conseq uence of an insufficient increase of insulin levels in response to intraven ous or oral glucose challenge. Important factors are the characteristics of the capsules applied in view of optimal diffusion kinetics, and the fact t hat an encapsulated islet graft can only be implanted in the peritoneal cav ity because of its volume. Further studies should focus on finding a practi cally applicable method to reduce the barrier between encapsulated islets a nd the bloodstream, in order to improve both the functional performance and the survival of encapsulated islet grafts.