Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways

K. Cardona, Z. Milas, E. Strobert, J. Cano, W. Jiang, S. A. Safley, S. Gangappa, B. J. Hering, C. J. Weber, T. C. Pearson, C. P. Larsen

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Recent advances in human allogeneic islet transplantation have established β-cell replacement therapy as a potentially viable treatment option for individuals afflicted with Type 1 diabetes. Two recent successes, one involving neonatal porcine islet xenografts transplanted into diabetic rhesus macaques treated with a costimulation blockade-based regimen and the other involving diabetic cynomolgus monkeys transplanted with adult porcine islet xenografts treated with an alternative multidrug immunosuppressive regimen have demonstrated the feasibility of porcine islet xenotransplantation in nonhuman primate models. In the current study, we assessed whether transplantation of adult porcine islet xenografts into pancreatectomized macaques, under the cover of a costimulation blockade-based immunosuppressive regimen (CD28 and CD154 blockade), could correct hyperglycemia. Our findings suggest that the adult porcine islets transplanted into rhesus macaques receiving a costimulation blockade-based regimen are not uniformly subject to hyperacute rejection, can engraft (2/5 recipients), and have the potential to provide sustained normoglycemia. These results provide further evidence to suggest that porcine islet xenotransplantation may be an attainable strategy to alleviate the islet supply crisis that is one of the principal obstacles to large-scale application of islet replacement therapy in the treatment of Type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)2260-2268
Number of pages9
JournalAmerican Journal of Transplantation
Volume7
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Costimulation blockade
  • Diabetes
  • Porcine islets
  • Xenotransplantation

Fingerprint

Dive into the research topics of 'Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways'. Together they form a unique fingerprint.

Cite this