Evaluation of Alginate Microcapsules for Use in Transplantation of Islets of Langerhans
Abstract: Transplantation of islets of Langerhans is a potential treatment of type 1 diabetes that aims to restore normal glucose homeostasis. Microencapsulation of islets could enable transplantation in the absence of immunosuppression, which would be beneficial as the side effects associated with immunosuppression outweigh the potential benefits of islet transplantation. Alginate is a polysaccharide that can be harvested from brown algae and is often used for microencapsulation of cells.The aim of this study was to evaluate alginate/poly-L-lysine/alginate capsules with regard to their biocompatibility and permeability to cytokines. Moreover, the function of microencapsulated islets was studied in vitro as well as their ability to reverse hyperglycaemia in diabetic mice.Microencapsulated rodent islets functioned well in vitro, with similar insulin release rates and glucose oxidation rates as naked islets. However, when cultured with interleukin-1? and tumour necrosis factor-?, microencapsulated islets were functionally suppressed, showing that the capsules are permeable to these cytokines. The biocompatibility of capsules varied depending on their composition. The presence of poly-L-lysine in the capsule decreased the biocompatibility. However, the biocompatibility of the capsules was improved when the coating alginate had been epimerised, i.e. enyzmatically tailored. Transplantation of microencapsulated allogeneic islets to immune competent mice lowered blood glucose concentrations up to 1 month after implantation. The success of the microencapsulated islet graft depended on the composition of the alginate/poly-L-lysine/alginate capsule used, as capsules that had poor biocompatibility failed to reverse hyperglycaemia more than transiently in athymic nude mice.In conclusion, alginate/poly-L-lysine/alginate capsules can protect islets of Langerhans from allogeneic rejection in mice. However, the composition of the capsule is of critical importance in the success of transplantation. Epimerised alginates may provide a novel capsule with ideal properties for microencapsulation of islets of Langerhans.
CLICK HERE TO DOWNLOAD THE WHOLE DISSERTATION. (in PDF format)