Alginate-based microcapsules for immunoprotected islet transplantation

Abstract

Islet transplantation is a promising therapeutic approach for the treatment of insulin-dependent diabetes mellitus. Nevertheless, its broader clinical use is hampered by the shortage of human organ donors as well as the need for a permanent immunosuppressive drug therapy in order to avoid rejection. Microencapsulation shall help to overcome this problem by creating an immunoprotected transplantation site. Biocompatibility of the encapsulation material and the possible immuno-interaction of the grafted tissue and the host immune system need to be examined very carefully. In transplantation experiments, we could show that the long-term function of the graft is dependent on the species of the islet donor, indicating that there has to be a recognition of the encapsulated islet despite the encapsulation membrane. This could be confirmed by in vitro data in the mixed lymphocyte islet culture (MLIC). Moreover, morphological studies of the tissue reaction toward encapsulated syngeneic vs. allogeneic vs. xenogeneic encapsulated islets reveal that the greater the difference between donor and recipient species the greater the amount of fibrous tissue formation. Thus, for the outcome of transplantation experiments, not only the material-related biocompatibility but as well the reaction towards the whole device (consisting of the capsule plus the encapsulated tissue) are crucial. Therefore, immunoprotection does not only comprise the protection of the grafted tissue from the host immune effector mechanisms but as well the inhibition of the recognition of the graft by the host immune system.