Complete protection of islets against allorejection and autoimmunity by a simple barium-alginate membrane.
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.
Duvivier-Kali
V F
VF
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA.
Omer
A
A
Parent
R J
RJ
O'Neil
J J
JJ
Weir
G C
GC
D000464:Alginates; D000818:Animals; D015551:Autoimmunity; D001672:Biocompatible Materials; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002214:Capsules; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000601:surgery*; D005951:Glucose Tolerance Test; D020723:Glucuronic Acid; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D006603:Hexuronic Acids; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D013370:Subrenal Capsule Assay; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic / Q000276:immunology
D000464:Alginates; D001672:Biocompatible Materials; D001786:Blood Glucose; D002096:C-Peptide; D002214:Capsules; D006603:Hexuronic Acids; D020723:Glucuronic Acid