The role of pathogen-associated molecular patterns and islet-derived danger-associated molecular patterns in longevity of microencapsulated pancreatic islets

Immunoisolation of cells by encapsulation in semipermeable membranes has been proposed as a cure for many endocrine diseases where a minute-to-minute regulation of metabolites is a requirement such as in anemia, dwarfism, kidney and liver failure, pituitary and central nervous system insufficiencies, and diabetes mellitus. The advantage of immunoisolation is that it allows for transplantation of cells in the absence of undesired permanent systemic immunosuppression. Also, it allows for transplantation of cells from non-human origin, i.e. xenografts, or cells generated from precursor or stem cells which may solve the problem of shortage of sufficient donor tissue.Immunoisolation is most intensively studied in application for treatment of type 1 diabetes. Although some success has been reported, graft function varies from several weeks to months, illustrating that some issues needs to be solved. In this thesis we studied the possible involvement of pathogen associated molecular patterns derived from encapsulation polymers and danger associated molecular patterns from pancreatic islets in failure of encapsulated islet grafts. The presence of these molecules may very per procedure, polymer and lab and might be responsible for the reported lab-to-lab variations, which is currently considered to be a major threat for clinical application