Immunobiology of liver xenotransplantation

Burcin Ekser; Christopher Burlak; Joshua P. Waldman; Andrew J. Lutz; Leela L. Paris; Massimiliano Veroux; Simon C. Robson; Michael A. Rees; David Ayares; Bruno Gridelli; A. Joseph Tector; David KC Cooper

doi:10.1586/eci.12.56

Immunobiology of liver xenotransplantation

Burcin Ekser, Christopher Burlak, Joshua P. Waldman, Andrew J. Lutz, Leela L. Paris, Massimiliano Veroux, Simon C. Robson, Michael A. Rees, David Ayares, Bruno Gridelli, A. Joseph Tector, David KC Cooper

Surgery

Research output: Contribution to journal › Review article › peer-review

23 Scopus citations

Abstract

Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- transgenic for human CD46, is associated with survival of approximately 7-9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a 'bridge' to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.

Original language	English (US)
Pages (from-to)	621-634
Number of pages	14
Journal	Expert Review of Clinical Immunology
Volume	8
Issue number	7
DOIs	https://doi.org/10.1586/eci.12.56
State	Published - Sep 2012

Bibliographical note

Funding Information:
D Ayares is an employee of Revivicor Inc. B Ekser is a recipient of a NIH NIAID T32 AI 074490 Training Grant. Work on xenotransplantation in the Thomas E. Starzl Transplantation Institute of the University of Pittsburgh, PA, USA, is supported in part by NIH grant U19 AI090959-01, and by Sponsored Research Agreements between the University of Pittsburgh and Revivicor, Inc., Blacksburg, VA, USA. Work on xenotransplantation at the University of Toledo Health Science Campus, OH, USA, is supported by NIH grant, 5R01DK066160-05. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Keywords

hCD46
liver
liver failure
nonhuman primate
pig
xenotransplantation
α1,3-galactosyltransferase gene-knockout

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10.1586/eci.12.56

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title = "Immunobiology of liver xenotransplantation",

abstract = "Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- transgenic for human CD46, is associated with survival of approximately 7-9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a 'bridge' to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.",

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note = "Funding Information: D Ayares is an employee of Revivicor Inc. B Ekser is a recipient of a NIH NIAID T32 AI 074490 Training Grant. Work on xenotransplantation in the Thomas E. Starzl Transplantation Institute of the University of Pittsburgh, PA, USA, is supported in part by NIH grant U19 AI090959-01, and by Sponsored Research Agreements between the University of Pittsburgh and Revivicor, Inc., Blacksburg, VA, USA. Work on xenotransplantation at the University of Toledo Health Science Campus, OH, USA, is supported by NIH grant, 5R01DK066160-05. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.",

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AU - Ekser, Burcin

AU - Burlak, Christopher

AU - Waldman, Joshua P.

AU - Lutz, Andrew J.

AU - Paris, Leela L.

AU - Veroux, Massimiliano

AU - Robson, Simon C.

AU - Rees, Michael A.

AU - Ayares, David

AU - Gridelli, Bruno

AU - Tector, A. Joseph

AU - Cooper, David KC

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AB - Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- transgenic for human CD46, is associated with survival of approximately 7-9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a 'bridge' to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.

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Immunobiology of liver xenotransplantation

Abstract

Bibliographical note

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