Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression.
BACKGROUND
This study assessed the capacity of alginate-encapsulated islets to reverse diabetes in a pig-to-primate model.


METHODS
Adult pig islets were encapsulated in microcapsules implanted under the kidney capsule (n=4) or in a subcutaneous macrodevice (n=5) in diabetic primates. Fasting blood glucose (FBG), insulin, porcine C-peptide, glycosylated hemoglobin (HbA1C), and cellular and humoral responses were followed.


RESULTS
Nonencapsulated pig islets were rejected within 7 days. A transient decrease of FBG was observed only during the 2 weeks after microencapsulated pig islet implantation under the kidney capsule. After subcutaneous transplantation of a macrodevice, diabetes was corrected up to a maximum of 6 months in five animals: FBG less than 107 mg/dL and HbA1C at 8% ± 1.4%. Two of the five animals received a new macrodevice between 25 and 35 weeks after the first graft dysfunction (HbA1C ≥ 13), and diabetes was controlled for an additional 18 weeks in these animals. Although a strong humoral response was elicited after transplantation of encapsulated islets, a total impermeability of alginate 3% wt/vol to IgG was demonstrated before and up to 20 weeks after transplantation of the subcutaneous macrodevice.


CONCLUSIONS
Pig islets encapsulated in a subcutaneous macrodevice can control diabetes up to 6 months without immunosuppression.
Dufrane
Denis
D
Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, Brussels, Belgium. denis.dufrane@uclouvain.be
Goebbels
Rose-Marie
RM
Gianello
Pierre
P
D000464:Alginates; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D020723:Glucuronic Acid; D006442:Glycated Hemoglobin / Q000378:metabolism; D006085:Graft Survival; D006603:Hexuronic Acids; D007165:Immunosuppression Therapy; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods* / Q000502:physiology; D008252:Macaca fascicularis; D040521:Subcutaneous Tissue / Q000601:surgery; D034421:Sus scrofa; D013997:Time Factors; D014183:Transplantation, Heterologous
D000464:Alginates; D000910:Antibodies, Heterophile; D001786:Blood Glucose; D002096:C-Peptide; D002214:Capsules; D020723:Glucuronic Acid; D006442:Glycated Hemoglobin; D006603:Hexuronic Acids; D007328:Insulin