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: 2.28). 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.

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    ABSTRACT: Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are 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. Pig insulin is biologically active in humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, differentiate and improve glucose tolerance in rhesus macaques without the need for immune suppression. Transplantation of embryonic pig pancreas is a novel approach towards beta cell replacement therapy that could be applicable to humans.
    Journal of Biomedical Science and Engineering 05/2013; 6(5A).
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    ABSTRACT: Here, we review the rationale for the use of organs from embryonic donors, antecedent investigations and recent work from our own laboratory, exploring the utility for transplantation of embryonic kidney and pancreas as an organ replacement therapy. Ultrastructurally precise kidneys differentiate in situ in rats following xenotransplantation in mesentery of embryonic pig renal primordia. The developing organ attracts its blood supply from the host. Engraftment of pig renal primordia requires host immune suppression. However, beta cells originating from embryonic pig pancreas obtained very early following initiation of organogenesis [embryonic day 28 (E28)] engraft long term in nonimmune-suppressed diabetic rats or rhesus macaques. Engraftment of morphologically similar cells originating from adult porcine islets of Langerhans occurs in animals previously transplanted with E28 pig pancreatic primordia. Organ primordia engraft, attract a host vasculature and differentiate following transplantation to ectopic sites. Attempts have been made to exploit these characteristics to achieve clinically relevant endpoints for end-stage renal disease and diabetes mellitus using animal models. We and others have focused on use of the embryonic pig as a donor.
    Current opinion in organ transplantation 02/2014; · 3.27 Impact Factor
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    Xenotransplantation 01/2013; 20(1):36-8. · 2.57 Impact Factor


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