Kidney xenotransplantation

Cowan, Peter J.; Cooper, David K. C.; d’Apice, Anthony J.F.

doi:10.1038/ki.2013.381

Cited by 42 publications

(31 citation statements)

References 159 publications

(166 reference statements)

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“…The use of pigs as organ donors became the focus of xenotransplantation, because pigs are plentiful, physiologically similar to humans, and less likely than primates to transmit zoonotic viruses (6). Hyperacute rejection was the survival-limiting barrier of pig-to-human xenografts, caused by preexisting xenoreactive antibodies and complement activation within the graft (7).…”

Section: Introductionmentioning

confidence: 99%

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Burlak

Paris

Lutz

et al. 2014

American Journal of Transplantation

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Xenotransplantation using genetically modified pig organs could solve the donor organ shortage problem. Two inactivated genes that make humans unique from pigs are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes were deleted in pigs human antibody binding was reduced in preliminary analysis. We analyzed the binding of human IgM and IgG from 121 healthy human serum samples for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells (PBMC). We analyzed a sub population for reactivity towards genetically modified pig PBMC as compared to chimpanzee and human PBMC. Deletion of the GGTA1 and CMAH genes in pigs improved the crossmatch results beyond those observed with chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig PBMC did not reveal a distinguishing feature such as blood group, age or gender. Modification of genes to make pig carbohydrates more similar to humans has improved the cross match with human serum significantly.

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Section: Introductionmentioning

confidence: 99%

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Burlak

Paris

Lutz

et al. 2014

American Journal of Transplantation

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“…Prevention of costimulation results in inhibition of the T cell response. The immunosuppressive regimens that have been tested in xenotransplantation models have demonstrated that the relatively new agents that are directed towards costimulation blockade are more effective than conventional immunosuppressive therapies (e.g., based on tacrolimus or cyclosporine) [30,31]. …”

Section: Pig-to-primate Organ Transplantationmentioning

confidence: 99%

Recent advances in understanding xenotransplantation: implications for the clinic

Cooper

Bottino

2015

Expert Review of Clinical Immunology

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Summary The results of organ and cell allotransplantation continue to improve, but the field remains limited by a lack of deceased donor organs. Xenotransplantation, e.g., between pig and human, offers unlimited organs and cells for clinical transplantation. The immune barriers include a strong innate immune response in addition to the adaptive T cell response. The innate response has largely been overcome by the transplantation of organs from pigs with genetic modifications that protect their tissues from this response. T cell-mediated rejection can be controlled by immunosuppressive agents that inhibit costimulation. Coagulation dysfunction between the pig and primate remains problematic but is being overcome by the transplantation of organs from pigs that express human coagulation-regulatory proteins. The remaining barriers will be resolved by the introduction of novel genetically-engineered pigs. Limited clinical trials of pig islet and corneal transplantation are already underway.

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“…In addition, porcine and human kidneys demonstrate similarities in the pathophysiology of ischemia reperfusion injury (IRI), biochemistry, and immunological parameters 14 . Thus, porcine renal transplantation is well-suited to investigate new organ preservation methods for marginal kidney grafts [15][16][17] , model human IRI 18 , study immunological pathways and allograft tolerance 19 , provide surgical training [20][21][22] , test new pharmacological therapies 23 , implement new medical devices, and study new immunological mechanisms in xenotransplantation [24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

Kaths

Echeverri

Goldaracena

et al. 2016

JoVE

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Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration.Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre-and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication. Video LinkThe video component of this article can be found at

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Kidney xenotransplantation

Cited by 42 publications

References 159 publications

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Recent advances in understanding xenotransplantation: implications for the clinic

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

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