Organogenetic tolerance

Hammerman, Marc R.

doi:10.4161/org.6.4.13283

Cited by 7 publications

(18 citation statements)

References 37 publications

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“…In the case of E28 embryonic pig pancreas, exocrine tissue does not differentiate following transplantation, obviating complications such as the enzymatic autodigestion of host tissues. [5][6][7][8][9][11][12][13][14] While glucose tolerance can be normalized in non-immunosuppressed diabetic rats by transplantation of E28 pig pancreatic primordia [5][6][7][8] and improved in rhesus macaques following transplantation of E28 pig pancreatic primordia 10 (Fig. 9A), it Figure 6.…”

Section: Discussionmentioning

confidence: 94%

“…Transplantation of embryonic pancreas (primordia) to replace the function of diseased organs offers theoretical advantages relative to transplantation of either pluripotent ES cells or of fully differentiated (adult) pancreas or islets: 10 (1) Primordia differentiate along defined organ-committed lines with no requirement to steer differentiation and no risk of teratoma formation. The glucose-sensing and insulin-releasing functions of β cells that differentiate from primordia are functionally linked; (2) The growth potential of cells within embryonic pancreas is enhanced relative to those in terminally differentiated pancreas or islets;…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] Cells originating from E28 pig pancreatic primordia engraft similarly in non immunosuppressed STZ-diabetic rhesus macaques, 9 and glucose tolerance is improved post-transplantation. 10 To ascertain whether engraftment of cells originating from E28 pig pancreatic primordia in rats is permissive for engraftment of the same or a similar cell component present in porcine islets from adult swine, we implanted the latter beneath the renal capsule of rats that previously had been transplanted with E28 pig pancreatic primordia in mesentery. Whole islets do not engraft.…”

Section: Engraftment Of Cells From Porcine Islets Of Langerhans Follomentioning

confidence: 99%

“…Intravenous glucose tolerance testing (IV GTT) was performed as before. 10 Exogenous insulin was held for 24 hours in macaques fasted for 18 hours prior to administration of glucose (0.5 g/kg) intravenously over 30 seconds as 50% dextrose. Peripheral venous blood samples were taken prior to injection (Time 0) and at several times after administration.…”

Section: Isolation Of Pig Pancreatic Primordia and Porcine Islets Andmentioning

confidence: 99%

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

et al. 2011

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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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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Engraftment Of Cells From Porcine Islets Of Langerhans Follomentioning

confidence: 99%

Section: Isolation Of Pig Pancreatic Primordia and Porcine Islets Andmentioning

confidence: 99%

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

et al. 2011

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“…Adaptation of this methodology for transplanting organs so as to induce organogenetic tolerance would revolutionize transplantation therapy [99].…”

Section: Future Perspectivementioning

confidence: 99%

Developing Immunologic Tolerance for Transplantation at the Fetal Stage

Mendieta-Zerón¹

2011

Immunotherapy

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Given the shortage of human organs for transplantation, the waiting lists are increasing annually and consequently so is the time and deaths during the wait. As most immune suppression therapy is not antigen specific and the risk of infection tends to increase, scientists are looking for new options for immunosuppression or immunotolerance. Tolerance induction would avoid the complications caused by immunosupressive drugs. As such, taking into account the experience with autoimmune diseases, one strategy could be immune modulation-induced changes in T-cell cytokine secretion or antigen therapy; however, most clinical trials have failed. Gene transfer of MHC genes across species may be used to induce tolerance to xenogenic solid organs. Other options are induction of central tolerance by the establishment of mixed chimerism through hematopoietic stem cell transplantation and the induction of 'operational tolerance' through immunodeviation involving dendritic or Tregs. I propose that, as the recognition and tolerance of proteins takes place in the thymus, this organ should be the main target for immunotolerance research protocols even as early as during the fetal development.

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Classic and current opinion in embryonic organ transplantation

Hammerman¹

2014

Current Opinion in Organ Transplantation

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Purpose of Review 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. Recent Findings Ultra structurally 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, insulin-producing cells originating from embryonic pig pancreas obtained very early following initiation of organogenesis [embryonic day 28 (E28)] engraft long term in non-immune 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. Summary 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.

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Organogenetic tolerance

Cited by 7 publications

References 37 publications

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

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

Developing Immunologic Tolerance for Transplantation at the Fetal Stage

Classic and current opinion in embryonic organ transplantation

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