Article

Engraftment of cells from porcine islets of Langerhans following transplantation of pig pancreatic primordia in non-immunosuppressed diabetic rhesus macaques

Washington University School of Medicine, St. Louis, MO, USA.
Organogenesis (Impact Factor: 2.6). 07/2011; 7(3):154-62. DOI: 10.4161/org.7.3.16522
Source: PubMed

ABSTRACT Transplantation therapy for human diabetes is limited by the toxicity of immunosuppressive drugs. If toxicity can be minimized, there will still be a shortage of human donor organs. Xenotransplantation of porcine islets is a strategy to overcome supply problems. Xenotransplantation in mesentery of pig pancreatic primordia obtained very early during organogenesis [embryonic day 28 (E28)] is a way to obviate the need for immunosuppression in rats or rhesus macaques and to enable engraftment of a cell component originating from porcine islets implanted beneath the renal capsule of rats. Here, we show engraftment in the kidney of insulin and porcine proinsulin mRNA-expressing cells following implantation of porcine islets beneath the renal capsule of diabetic rhesus macaques transplanted previously with E28 pig pancreatic primordia in mesentery. Donor cell engraftment is confirmed using fluorescent in situ hybridization (FISH) for the porcine X chromosome and is supported by glucose-stimulated insulin release in vitro. Cells from islets do not engraft in the kidney without prior transplantation of E28 pig pancreatic primordia in mesentery. This is the first report of engraftment following transplantation of porcine islets in non-immunosuppressed, immune-competent non-human primates. The data are consistent with tolerance to a cell component of porcine islets induced by previous transplantation of E28 pig pancreatic primordia.

0 Followers
 · 
169 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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 non-immune, suppressed diabetic rats or rhesus macaques. Morphologically, similar cells originating from adult porcine islets of Langerhans (islets) engraft in non-immune-suppressed rats or rhesus macaques previously transplanted with E28 pig pancreatic primordia. Our data are consistent with induction of tolerance to an endocrine cell component of porcine islets induced by previous transplantation of embryonic pig pancreas, a novel finding we designate organogenetic tolerance. The potential exists for its use to enable the use of pigs as islet cell donors for humans with no immune suppression requirement.
    Journal of Transplantation 09/2011; 2011(2090-0007):261352. DOI:10.1155/2011/261352
  • [Show abstract] [Hide abstract]
    ABSTRACT: Schneider MKJ, Seebach JD. Xenotransplantation literature update, November-December 2011. Xenotransplantation 2012; 19; 65-69. © 2012 John Wiley & Sons A/S.
    Xenotransplantation 01/2012; 19(1):65-9. DOI:10.1111/j.1399-3089.2012.00692.x · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Organogenesis 04/2012; 8(2):41-8. DOI:10.4161/org.20930 · 2.60 Impact Factor
Show more