Isolation, transplantation, and functional studies of adult porcine islets of Langerhans.
Transplantation of islets of Langerhans is a possible treatment for type-I diabetes mellitus. However, there is a shortage of donors for such transplantations and the pig may be an alternative source of donor organs. The aims of the study reported here were to establish a method for adult porcine islet isolation that was based on enzymatic digestion using Liberase PI in a semiautomatic set-up, and to evaluate the in vitro and in vivo function of isolated islets. After overnight culture, isolated islets, from five of seven batches, had poor insulin response to an in vitro glucose challenge that was only partially increased by additional challenge with arginine. More than 50% of DNA and 90% of the insulin content was lost during a one-week culture period. With some batch-to-batch variation, in 15 of 25 cases, 4,000 to 7,000 porcine islets cured streptozotocin diabetic nude mice within three weeks following transplantation. In conclusion, it is possible to isolate viable islets from adult pigs, using a semiautomatic set-up. With batch-to-batch variation, the islets are able to revert diabetes mellitus when transplanted to diabetic nude mice.
Nielsen
Thomas Buschmann
TB
Department of Medical Endocrinology/Biomedical Laboratory, Odense University Hospital, Denmark.
Yderstraede
Knud Bonnet
KB
Beck-Nielsen
Henning
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013552:Swine
D007328:Insulin; D004247:DNA; D001120:Arginine; D005947:Glucose