Affiliation:
1. From the Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
Abstract
Differentiation and maturation of porcine neonatal pancreatic cell clusters (NPCCs) microencapsulated in barium alginate were assessed after transplantation into immunocompetent mice. Microencapsulated NPCCs were transplanted into the peritoneal cavity of streptozocin-induced diabetic B6AF1 mice (n = 32). The microcapsules were removed at 2, 6, and 20 weeks and examined for cellular overgrowth, insulin content, and insulin secretory responses to glucose and glucose with theophylline. The differentiation, maturation, and proliferation of the β-cells in the NPCCs were assessed by immunohistochemistry. Blood glucose levels were normalized in 81% of the animals that received a transplant and remained normal until termination of the experiments at 20 weeks. Hyperglycemic blood glucose levels after explantation of the capsules confirmed the function of the encapsulated NPCCs. Insulin content of the encapsulated NPCCs was increased 10-fold at 20 weeks after transplantation compared with pretransplantation levels. A 3.2-fold increase of the ratio of the β-cell area to the total cellular area was observed at 20 weeks, demonstrating the maturation of NPCCs into β-cells. In conclusion, NPCCs encapsulated with simple barium alginate can differentiate into β-cells and reverse high blood glucose levels in immunocompetent mice without immunosuppression for >20 weeks.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference26 articles.
1. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343: 230–238,2000
2. Weir GC, Bonner-Weir S: Scientific and political impediments to successful islet transplantation. Diabetes 46: 1247–1256,1997
3. Lanza RP, Jackson R, Sullivan A, Ringeling J, McGrath C, Kuhtreiber W, Chick WL: Xenotransplantation of cells using biodegradable microcapsules. Transplantation 67: 1105–1111,1999
4. Sun Y, Ma X, Zhou D, Vacek I, Sun AM: Normalization of diabetes in spontaneously diabetic cynomolgus monkeys by xenografts of microencapsulated porcine islets without immunosuppression. J Clin Invest 98: 1417–1422,1996
5. Lanza RP, Kuhtreiber WM, Ecker DM, Marsh JP, Chick WL: Successful bovine islet xenografts in rodents and dogs using injectable microreactors. Transplant Proc 27: 3211,1995
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