Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane Valérie F. Duvivier-Kali , Abdulkadir Omer , Richard J. Parent , John J. O’Neil and Gordon C. Weir Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, Massachusetts Abstract We describe a new technique for microencapsulation with high–mannuronic acid (high-M) alginate crosslinked with BaCl 2 without a traditional permselective component, which allows the production of biocompatible capsules that allow prolonged survival of syngeneic and allogeneic transplanted islets in diabetic BALB/c and NOD mice for >350 days. The normalization of the glycemia in the transplanted mice was associated with normal glucose profiles in response to intravenous glucose tolerance tests. After explantation of the capsules, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated islets. The retrieved capsules were free of cellular overgrowth and islets responded to glucose stimulation with a 5- to 10-fold increase of insulin secretion. Transfer of splenocytes isolated from transplanted NOD mice to NOD/SCID mice adoptively transferred diabetes, indicating that NOD recipients maintained islet-specific autoimmunity. In conclusion, we have developed a simple technique for microencapsulation that prolongs islet survival without immunosuppression, providing complete protection against allorejection and the recurrence of autoimmune diabetes. Footnotes Address correspondence and reprint requests to Gordon C. Weir, MD, Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: gordon.weir{at}joslin.harvard.edu . Received for publication 26 April 2001 and accepted 21 May 2001. Posted on the World Wide Web at www.diabetes.org/diabetes on 21 June 2001. IE, islet equivalent; IFN, γ-interferon; IL, interleukin; IVGTT, intravenous glucose tolerance test; PLL, poly- l -lysine; RIA, radioimmunoassay; STZ, streptozotocin.