STRUCTURE AND FUNCTION OF MACROENCAPSULATED HUMAN AND RODENT PANCREATIC-ISLETS TRANSPLANTED INTO NUDE-MICE

Macroencapsulation of human pancreatic islets inside biomembranes is a promising approach to maintain islet allografts in the diabetic recip ient without immunosuppression. In order to test this possibility isle ts isolated from human pancreata were kept in culture before macroenca psulation in a tissue chamber device. The device consisted of two tita nium rings, which supported two flat membranes. These membranes have p reviously been shown to protet pancreatic islets and fetal lung tissue from allograft rejection and also to promote neovascularization at th e membrane surface. In a first series of experiments macroencapsulated human islets were implanted into the epididymal fat pad of athymic, n ude mice concomitant to an injection from the same batch of islets und er the kidney capsule. Light microscopy of encapsulated and subcapsula rly grafted human islets showed that the survival inside the membranes was as good as under the kidney capsule. There was an extensive forma tion of new blood vessels at the membrane outer surface. In a second s eries of experiments insulin was extracted from encapsulated human isl ets implanted either into the epididymal fat pad or subcutaneously, Th e encapsulated human islets contained as much insulin as the nonencaps ulated ones, In these experiments mouse and rat islets were also used, Rodent islets, however, survived less well than the human islets as e videnced by the markedly reduced insulin content values. In a third se ries of experiments human islets were loaded into the chambers and tra nsplanted into nude mice without the concomitant implantation of non-e ncapsulated islets under the kidney capsule of the recipienets. Measur ements of human C-peptide in serum samples obtained 4 to 8 weeks post- implantation showed considerable concentrations (0.70-185 ng/ml) in al l animals. We conclude that isolated human islets survive when implant ed into nude mice and continue to release insulin for several weeks. T here are, however, species differences suggesting that rodent islets a re much more susceptible to the environmental stress inside the membra nes than human islets.