Abstract
We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulation blockade regimen achieved sustained insulin independence (median survival, >140 days) without evidence of porcine endogenous retrovirus dissemination. Thus, neonatal porcine islets represent a promising solution to the crucial supply problem in clinical islet transplantation.
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Acknowledgements
This work was supported by the Juvenile Diabetes Research Foundation Center Grant 6-2005-1328, and the US National Institutes of Health grant U19-AI51731 with additional support from the Yerkes Base Grant P51-RR000165-45, the McKelvey Lung Transplant Center, and the Carlos and Marguerite Mason Trust as support for C.P.L. In addition, R.V.R. was supported by the Canadian Institutes of Health Research grant FRN-8030, Edmonton Civic Employees Charitable Assistance Fund, Alberta Diabetes Foundation, and University Hospital Foundation MacLachlan Fund. G.S.K. received a Career Development Award from the JDRF and a Senior Scholarship from the Alberta Heritage Foundation for Medical Research. We are indebted to the Yerkes veterinary staff, in particular, D. Anderson, R. Fest and M. Hossfield, for their support. We also thank K. Kite-Powell for editorial comments. Belatacept and H106 (CD154-specific antibody) for these studies were provided by Bristol-Myers Squibb.
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Christian P. Larsen and Thomas C. Pearson have received consulting fees from Bristol-Myers Squibb, Pfizer and Abbott and grant support from Bristol-Myers Squibb, Novartis and Abegenix and have assigned all future royalties relating to US patent 5,916,560, “Methods for inhibiting an immune response by blocking the GP39/CD40 and CTLA4/CD28/B7 pathways and compositions for use therewith,” issued jointly to Bristol-Myers Squibb and Emory University, to Emory University.
Supplementary information
Supplementary Fig. 1
Experimental scheme of transplant experiments. (PDF 37 kb)
Supplementary Fig. 2
Assessment of anti-Gal and total anti-pig IgG. (PDF 52 kb)
Supplementary Table 1
Cohorts, survival, and characterization of neonatal porcine islets. (PDF 27 kb)
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Cardona, K., Korbutt, G., Milas, Z. et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med 12, 304–306 (2006). https://doi.org/10.1038/nm1375
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DOI: https://doi.org/10.1038/nm1375
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