NOVEL DELIVERY OF PANCREATIC-ISLET CELLS TO TREAT INSULIN-DEPENDENT DIABETES-MELLITUS

Immune protective devices containing pancreatic islets are designed to treat insulin-dependent diabetes mellitus by providing glycaemic cont rol without immunosuppression. The immune protection is achieved by se parating allogeneic or xenogeneic islets from the host by semipermeabl e membranes that allow only small molecules such as glucose, insulin a nd nutrients to pass through. Lymphocytes and immunoglobulins are excl uded by the membrane and unable to cause rejection of the islets. Thre e types of immune protective devices, i.e. microcapsules, diffusion ch ambers and perfusion devices (vascularised artificial pancreas), have been studied. Microcapsules injected into the abdominal cavity in a la rge quantity achieved glycaemic control, but required a small amount o f immunosuppression to prevent fibrosis around the capsules. A clinica l attempt to use microcapsulated human islets in a diabetic patient wh o has maintained functional kidney allografts has been reported. Intra -abdominal placement of diffusion chambers containing allogeneic islet s achieved excellent glycaemic control without immunosuppression in di abetic dogs. However, their use was limited by the eventual breakage o f tubular chambers. We have extensively used the vascularised artifici al pancreas for treatment of experimental diabetes mellitus. Excellent biocompatibility of the device was evidenced by the extraordinary lon gevity of the patency of the device in healthy dogs. Long term control of severe diabetes mellitus Was achieved in totally pancreatectomised dogs without immunosuppression by devices seeded with allogeneic (can ine) and xenogeneic (porcine) islets. The vascularised artificial panc reas could be an excellent alternative to Diabetes Control and Complic ation Trial (DCCT)-type intensive insulin therapy or pancreatic transp lantation by providing tight glycaemic control with minimal exogenous insulin therapy without immunosuppression.