Transplantation of Free and Microencapsulated Islets in Rats: Evidence for the Requirement of An Increased Islet Mass for Transplantation into the Peritoneal Site

Abstract

Microencapsulation of islets of Langerhans may avoid the necessity of a permanent immunosuppressive drug therapy and opens up new perspectives for xenotransplantation in the treatment of insulin dependent diabetes. In a mouse model we recently showed long-term normoglycemia after microencapsulated xenotransplantation. Since the acceptance of mice to any kind of foreign material is quite high we assume that the rat model better reflects the situation of higher mammalians or even humans. Due to the volume of the transplanted material (i.e. islets+alginate-capsule) only the peritoneal cavity can be used up to now. The quantity of islets necessary to normalize the non-fasting blood glucose level was much higher than expected and free transplants needed even a higher amount of islets than encapsulated ones (3000 encapsulated vs. 2 x 3000 non-encapsulated). Transplantation beneath the kidney capsule was successful with only 1200-1500 islets per rat proving the metabolic potency of the islets. Implantation of empty capsules did not alter the diabetic state. We conclude that the alginate matrix may act as a "spacer" creating a distance between the consuments of a lacking substrate esp. oxygen in an unfavourable environment and perhaps protect it from unspecific mediators released during the postoperative period. Our findings underline the necessity for smaller capsules that would enable us to use other transplantation sites.