Survival of microencapsulated adult pig islets in mice in spite of an antibody response.
The aim of this study was to assess the capacity of simple alginate capsules to protect adult pig islets in a model of xenotransplantation. Adult pig islets were microencapsulated in alginate, with either single alginate coats (SAC) or double alginate coats (DAC), and transplanted into the streptozotocin-induced diabetic B6AF1 mice. Normalization of glucose levels was associated with an improvement of the glucose clearance during intravenous glucose tolerance tests. After explantation, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated pig islets. Explanted capsules were mainly free of fibrotic reaction and encapsulated islets were still functional, responding to glucose stimulation with a 10-fold increase in insulin secretion. However, a significant decrease in the insulin content and insulin responses to glucose was observed for encapsulated islets explanted from hyperglycemic mice. An immune response of both IgG and IgM subtypes was detectable after transplantation. Interestingly, there were more newly formed antibodies in the serum of mice transplanted with SAC capsules than in the serum of mice transplanted with DAC capsules. In conclusion, alginate capsules can prolong the survival of adult pig islets transplanted into diabetic mice for up to 190 days, even in the presence of an antibody response.
Duvivier-Kali
Valérie F
VF
Diabetes and Obesity Unit, Sanofi Synthelabo, Rueil-Malmaison, France.
Omer
Abdulkadir
A
Lopez-Avalos
Maria D
MD
O'Neil
John J
JJ
Weir
Gordon C
GC
D000818:Animals; D000917:Antibody Formation; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D006085:Graft Survival / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D001786:Blood Glucose; D002214:Capsules; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007328:Insulin