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Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways

Nature Medicine volume 12, pages 304–306 (2006)Cite this article

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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Figure 1: Assessment of neonatal porcine islet xenograft function in pancreatectomized rhesus macaques.
Figure 2: Immunohistochemical assessment of neonatal porcine islet xenografts and viral monitoring in transplant recipients.

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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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Author notes

  1. Kenneth Cardona and Gregory S Korbutt: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Emory Transplant Center, Emory University School of Medicine, 101 Woodruff Circle, Suite 5105, Atlanta, 30322, Georgia, USA

    Kenneth Cardona, Zvonimir Milas, Jose Cano, Wanhong Jiang, Hameeda Bello-Laborn, Shivaprakash Gangappa, Collin J Weber, Thomas C Pearson & Christian P Larsen

  2. Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, T6G 2N8, Alberta, Canada

    Gregory S Korbutt, James Lyon, Brad Hacquoil & Ray V Rajotte

  3. Yerkes National Primate Research Center, Emory University School of Medicine, 954 Gatewood Road, Atlanta, 30322, Georgia, USA

    Elizabeth Strobert

Authors
  1. Kenneth Cardona
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  2. Gregory S Korbutt
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Corresponding authors

Correspondence to Ray V Rajotte or Christian P Larsen.

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Competing interests

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)

Supplementary Methods (PDF 94 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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