TY - JOUR
T1 - 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
AU - Hirshberg, Boaz
AU - Montgomery, Sean
AU - Wysoki, Michael G.
AU - Xu, He
AU - Tadaki, Doug
AU - Lee, Janet
AU - Hines, Kenneth
AU - Gaglia, Jason
AU - Patterson, Noelle
AU - Leconte, John
AU - Hale, Douglas
AU - Chang, Richard
AU - Kirk, Alan D.
AU - Harlan, David M.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036303155&partnerID=8YFLogxK
U2 - 10.2337/diabetes.51.7.2135
DO - 10.2337/diabetes.51.7.2135
M3 - Article
C2 - 12086943
AN - SCOPUS:0036303155
SN - 0012-1797
VL - 51
SP - 2135
EP - 2140
JO - Diabetes
JF - Diabetes
IS - 7
ER -