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.
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.
Hirshberg
Boaz
B
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
Montgomery
Sean
S
Wysoki
Michael G
MG
Xu
He
H
Tadaki
Doug
D
Lee
Janet
J
Hines
Kenneth
K
Gaglia
Jason
J
Patterson
Noelle
N
Leconte
John
J
Hale
Douglas
D
Chang
Richard
R
Kirk
Alan D
AD
Harlan
David M
DM
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
D001786:Blood Glucose; D002096:C-Peptide; D001120:Arginine