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

Nat Med. 2006 Mar;12(3):301-3. doi: 10.1038/nm1369. Epub 2006 Feb 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / surgery*
  • Graft Rejection / immunology
  • Graft Survival / immunology
  • Immunosuppression*
  • Islets of Langerhans / cytology
  • Islets of Langerhans Transplantation*
  • Macaca / immunology*
  • Macaca / surgery*
  • Portal System / immunology
  • Swine*
  • Transplantation, Heterologous*