Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways.
Recent advances in human allogeneic islet transplantation have established beta-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.
Cardona
K
K
Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
Milas
Z
Z
Strobert
E
E
Cano
J
J
Jiang
W
W
Safley
S A
SA
Gangappa
S
S
Hering
B J
BJ
Weber
C J
CJ
Pearson
T C
TC
Larsen
C P
CP
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D000068800:Etanercept; D006493:Heparin / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000502:physiology*; D008253:Macaca mulatta; D015166:Monitoring, Immunologic; D010180:Pancreatectomy; D011323:Primates; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D006493:Heparin; D000068800:Etanercept