Structure and Function of Macroencapsulated Human and Rodent Pancreatic Islets Transplanted into Nude Mice

Abstract

Macroencapsulation of human pancreatic islets inside biomembranes is a promising approach to maintain islet allografts in the diabetic recipient without immunosuppression. In order to test this possibility islets isolated from human pancreata were kept in culture before macroencapsulation in a tissue chamber device. The device consisted of two titanium rings, which supported two flat membranes. These membranes have previously been shown to protet pancreatic islets and fetal lung tissue from allograft rejection and also to promote neovascularization at the membrane surface. In a first series of experiments macroencapsulated human islets were implanted into the epididymal fat pad of athymic, nude mice concomitant to an injection from the same batch of islets under the kidney capsule. Light microscopy of encapsulated and subcapsularly grafted human islets showed that the survival inside the membranes was as good as under the kidney capsule. There was an extensive formation of new blood vessels at the membrane outer surface. In a second series of experiments insulin was extracted from encapsulated human islets implanted either into the epididymal fat pad or subcutaneously. The encapsulated human islets contained as much insulin as the non-encapsulated ones. In these experiments mouse and rat islets were also used. Rodent islets, however, survived less well than the human islets as evidenced by the markedly reduced insulin content values. In a third series of experiments human islets were loaded into the chambers and transplanted into nude mice without the concomitant implantation of non-encapsulated islets under the kidney capsule of the recipienets. Measurements of human C-peptide in serum samples obtained 4 to 8 weeks post-implantation showed considerable concentrations (0.70 - 185 ng/ml) in all animals. We conclude that isolated human islets survive when implanted into nude mice and continue to release insulin for several weeks. There are, however, species differences suggesting that rodent islets are much more susceptible to the environmental stress inside the membranes than human islets.

Key words

Pancreatic Islets - Microencapsulation - Biomembranes - Islet Allografts