title: Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site.
abstract: We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated 20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either the portal vein (n = 6) or the celiac artery (n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments, animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed even transient insulin independence (P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection, however, does not appear to be a viable islet transplantation technique.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases/Navy Transplantation & Autoimmunity Branch, NIH, Building 10 Rm. 11S219, 10 Center Drive, Bethesda, MD 10889, USA. boazh@intra.niddk.nih.gov
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.forename: Sean
authors.initials: S
authors.lastname: Montgomery
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wysoki
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.forename: Doug
authors.initials: D
authors.lastname: Tadaki
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hines
authors.forename: Jason
authors.initials: J
authors.lastname: Gaglia
authors.forename: Noelle
authors.initials: N
authors.lastname: Patterson
authors.forename: John
authors.initials: J
authors.lastname: Leconte
authors.forename: Douglas
authors.initials: D
authors.lastname: Hale
authors.forename: Richard
authors.initials: R
authors.lastname: Chang
authors.forename: Alan D
authors.initials: AD
authors.lastname: Kirk
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002445:Celiac Artery; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D006084:Graft Rejection; D006085:Graft Survival; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000473:pathology / Q000502:physiology; D008253:Macaca mulatta; D009929:Organ Size; D011169:Portal Vein; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D001120:Arginine