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Brief Communication
Nature Medicine - 12, 301 - 303 (2006)
Published online: 19 February 2006; | doi:10.1038/nm1369

Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates

Bernhard J Hering1, Martin Wijkstrom1, Melanie L Graham1, Maria Hårdstedt1, Tor C Aasheim1, Tun Jie1, Jeffrey D Ansite1, Masahiko Nakano1, Jane Cheng2, Wei Li2, Kathleen Moran2, Uwe Christians3, Colleen Finnegan4, Charles D Mills1, David E Sutherland1, Pratima Bansal-Pakala1, Michael P Murtaugh4, Nicole Kirchhof5 & Henk-Jan Schuurman2

1  Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, 424 Harvard Street SE, Minneapolis, Minnesota 55455, USA.

2  Immerge BioTherapeutics, Inc., Building 75, Third Avenue, Charlestown, Massachusetts 02129, USA.

3  Department of Anesthesia, University of Colorado Health Sciences Center, 4200 East 9th Avenue B113, Denver, Colorado 80262, USA.

4  Department of Veterinary and Biomedical Sciences, University of Minnesota, 205 Veterinary Science Building, 1971 Commonwealth Avenue, St. Paul, Minnesota 55108, USA.

5  Department of Veterinary Population Medicine, 225 Veterinary Medical Center, 1365 Gortner Avenue, University of Minnesota, St. Paul, Minnesota 55108, USA.

Correspondence should be addressed to Bernhard J Hering bhering@umn.edu

Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.

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The right stuff: Breaking through the xenotransplant barrier

Nature Medicine News and Views (01 Nov 1996)

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ISSN: 1078-8956
EISSN: 1546-170X
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