Barium-cross-linked alginate beads: a simple, one-step method for successful immunoisolated transplantation of islets of Langerhans

Transplantation of xenogeneic islets in immunoisolating membranes may solve the problems of the availability of human donor organs and long-term immunosuppression. Alginates are widely used for microencapsulation of isolated islets. This study presents data of a new method in which alginate was cross-linked with barium ions. In the perifusion experiment microencapsulated rat islets showed a biphasic insulin release with a short delay of the first phase. During static glucose challenge the insulin release ranged from 40% to 70% compared to free floating controls. In 3 of 11 diabetic mice, transplantation of 800 barium-alginate-bead encapsulated rat islets resulted in a non-fasting normoglycaemia at least up to 70 days. In the same model, transplantation of 3000 encapsulated porcine islets resulted in 6 of 10 recipients in normoglycaemia up to day 70, while 3 animals were still normoglycaemic on day 100. On day 21 after transplantation of encapsulated rat and porcine islets and intraperitoneal glucose tolerance test revealed rapid glucose assimilation in both groups. Histological examination demonstrated well-preserved islets at the end of the experiments. Immunohistological B-cell staining revealed the absence of recruitment of β-cells in the recipient's own pancreas. The barium-alginate microencapsulation method represents a simple one-step method for effective immunoisolated transplantation of large-scale islet preparations.