Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice.
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 beta-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 beta-cell area to the total cellular area was observed at 20 weeks, demonstrating the maturation of NPCCs into beta-cells. In conclusion, NPCCs encapsulated with simple barium alginate can differentiate into beta-cells and reverse high blood glucose levels in immunocompetent mice without immunosuppression for >20 weeks.
Omer
Abdulkadir
A
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Duvivier-Kali
Valérie F
VF
Trivedi
Nitin
N
Wilmot
Karen
K
Bonner-Weir
Susan
S
Weir
Gordon C
GC
D000464:Alginates; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D002214:Capsules; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D016922:Cellular Senescence; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005951:Glucose Tolerance Test; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007121:Immunocompetence; D007074:Immunoglobulin G / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous
D000464:Alginates; D001786:Blood Glucose; D002214:Capsules; D006603:Hexuronic Acids; D007074:Immunoglobulin G; D020723:Glucuronic Acid