Survival and Maturation of Microencapsulated Porcine Neonatal Pancreatic Cell Clusters Transplanted into Immunocompetent Diabetic Mice
- Abdulkadir Omer,
- Valérie F. Duvivier-Kali,
- Nitin Trivedi,
- Karen Wilmot,
- Susan Bonner-Weir and
- Gordon C. Weir
- From the Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
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.
Address correspondence and reprint requests to Gordon C. Weir, M.D., Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail:.
Received for publication 24 May 2002 and accepted in revised form 30 September 2002.
CK, cytokeratin; FITC, fluorescein isothiocyanate; IVGTT, intravenous glucose tolerance test; NPCC, neonatal pancreatic cell cluster; PLL, poly-L-lysine; RT, room temperature; STZ, streptozotocin.