FEASIBILITY OF AGAROSE MICROBEADS WITH XENOGENEIC ISLETS AS A BIOARTIFICIAL PANCREAS

A bioartificial pancreas, that is, transplantation of islets of Langer hans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immune-is olated from the host by the semipermeable membrane preventing rejectio n while maintaining control of glucose metabolism for an extended peri od. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a b ioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combinatio n of encapsulation of hamster islets in 5% agarose microbeads and in v itro culture of them prolonged xenograft survivals. Four of 6 recipien ts were still normoglycemic at 100 days after implantation. However, t he same procedure was not effective in the recipients which were sensi tized in advance by transplantation of free hamster islets and thus ha d high levels of anti-hamster antibodies. The average normoglycemic pe riod was 32 days. Antibodies permeated through the microbeads and acti vated complement on the cell surfaces. The network of agarose microbea ds was rendered dense by increasing the concentration of agarose to re strict the diffusion of antibodies. Graft survivals were prolonged wit h increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplan tation was enabled by the combination of the microbeads with a concent ration of agarose higher than 7.5% and in vitro culture even in recipi ents having a high level of preformed antibodies. (C) 1994 John Wiley and Sons, Inc.