Transplantation of pancreatic islets contained in minimal volume microcapsules in diabetic high mammalians.
To minimize technical problems relating to excessive size (600-800 mu in diameter) of standard alginate microcapsules (CSM) for pancreatic islet graft immunoisolation, we have developed two novel minimal volume, chemically identical, capsule prototypes (MVC): 1) coherent microcapsules (CM), and 2) medium-size microcapsules (300-400 mu, MSM). CM, which envelop each individual islet within a thin alginate hydrogel cast, are prepared by emulsification, whereas MSM are made by atomizing the islet-alginate suspension through a special microdroplet generator. Upon graft into diabetic rodents, CM have shown to immunoprotect both allo- and xenogeneic nondiscordant islets, and restored normoglycemia. In higher mammals, at subtherapeutic doses, CM fully immunoprotected islet allografts (pig-->pig), but only temporarily xenografts (dog-->pig). We then used MSM to immunoisolate canine islet allografts in the peritoneal cavity of dogs with spontaneous insulin-dependent diabetes. Of three grafted dogs, two showed full remission of hyperglycemia with insulin withdrawal. MSM could represent an intermediate solution between CSM and CM for peritoneal immunoisolated islet transplants.
Calafiore
R
R
Department of Internal Medicine, University of Perugia, Italy. islet@unipg.it
Basta
G
G
Luca
G
G
Boselli
C
C
Bufalari
A
A
Bufalari
A
A
Cassarani
M P
MP
Giustozzi
G M
GM
Brunetti
P
P
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy* / Q000662:veterinary; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D011786:Quality Control; D013552:Swine; D014183:Transplantation, Heterologous