Strategy for developing microbeads applicable to islet xenotransplantation into a spontaneous diabetic NOD mouse

A bioartificial pancreas (BAP) created through the encapsulation of islets of Langerhans (islets) in a semipermeable membrane has been proposed as a promising approach to treating insulin-dependent diabetes patients. A nonobese diabetic (NOD) mouse, which shares many features of human insulin-dependent diabetes mellitus, is an ideal model for evaluating the function of BAP. However, the functions of BAPs that have been developed have been limited in NOD mice. We propose novel microbeads that can realize long-term BAP function in NOD mice. The novel microbeads were composed of agarose and poly(styrene sulfonic acid) (PSSa) mixed gel. A polyion complex layer between PSSa and polycationic polybrene was formed on and just inside the microbead, and the microbead surfaces were further covered by polyanions to produce anionic surface charges. The islets in the novel microbeads were intraperitoneally implanted. Graft-functioning periods were dependent on both PSSa concentration and the kinds of polyanion. Islets in the microbeads composed of 5% agarose and 5% PSSa, which had an outermost surface covered by carboxymethyl cellulose, produced normoglycemic periods of more than 60 days in all five recipients. Control mice receiving either transplants of unenclosed islets or islets in agarose microbeads showed normoglycemic periods of less than 12 days. We believe that agarose/PSSa microbeads are promising for producing semipermeable membranes that enable xenotransplantation of islets in spontaneous diabetes mellitus.