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

被引:33
作者
Hirshberg, B
Montgomery, S
Wysoki, MG
Xu, H
Tadaki, D
Lee, J
Hines, K
Gaglia, J
Patterson, N
Leconte, J
Hale, D
Chang, R
Kirk, AD
Harlan, DM
机构
[1] NIDDK, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA
[2] Yale Univ, Dept Radiol, New Haven, CT USA
[3] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA
[4] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA
关键词
D O I
10.2337/diabetes.51.7.2135
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:2135 / 2140
页数:6
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