Transplantation of Pancreatic Islet in an Immunoisolation Device

Abstract

Background: Type-1 diabetes is caused by autoimmune destruction of insulin-producing B-cells in the pancreas. Today, transplantation of whole pancreas or islets is the only treatment that can restore endogenous insulin production. Within the past 20 years, pancreatic islet transplantation has become a clinical reality and an option in diabetes treatment. However, large use of this therapy is limited by shortage in organ donations and use of immunosuppressive drugs. Immunoisolation potentially allows elimination of immunosuppressive drugs and use of xenogenic tissue solving the problem of a shortage in organ donation. Aims: The present work was designed to ameliorate isolation of islets from different species and encapsulation of islets in immunoisolation devices (hollow fibres and microcapsules). Moreover, a mathematical model for immunoisolation membrane selection was developed. Results and Conclusions: The application of the automated method allows significant increase in the number of islets obtained. These islets were then used for in vitro or in vivo studies of immunoisolation devices, tested in different protocols. Experimental results indicate that islet transplantation using alginate gel microcapsule in the peritoneal cavity successfully control glycaemia in diabetic animals. However, it is not possible to translate in human application for the implantation site. An alternative strategy was developed based on membrane device to be used in the subcutaneous space. Despite permeability properties have been proved to be adequate, the in vivo functional response of transplanted islet in hollow fibre device was only temporary, probably for development of fibrotic tissue around the device. Future work: The use of theoretical model allows evaluation and selection of new membrane materials for islet immunoisolation. Efficacy of new devices would be determined by performing allo- or xeno- transplantations into diabetic recipients, exploring new sites of implantation that minimize surgical procedures and reduce implant failure.