Development of a novel xenotransplantation strategy for treatment of diabetes mellitus in rat hosts and translation to non-human primates.
Transplantation therapy for diabetes is limited by unavailability of donor organs and outcomes complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in inbred diabetic Lewis or Zucker Diabetic Fatty (ZDF) rats or rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, normalize glucose tolerance in rats and improve glucose tolerance in rhesus macaques without the need for immune suppression. Engraftment of primordia is permissive for engraftment of an insulin-expressing cell component from porcine islets implanted subsequently without immune suppression. Similarities between findings in inbred rat and non-human primate hosts bode well for successful translation to humans of what could be a novel xenotransplantation strategy for the treatment of diabetes.
George M. O'Brien Center for Kidney Disease Research, Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO USA. mhammerm@dom.wustl.edu
Marc R
MR
Hammerman
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002465:Cell Movement; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D004622:Embryo, Mammalian; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D008198:Lymph Nodes / Q000473:pathology; D008253:Macaca mulatta; D008643:Mesentery / Q000276:immunology / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D013552:Swine; D014183:Transplantation, Heterologous
D001786:Blood Glucose