Immunobiology of liver xenotransplantation

Burcin Ekser Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy; Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy

Christopher Burlak Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA

Joshua P Waldman Department of Urology, University of Toledo Health Sciences Campus, Toledo, OH, USA; Department of Urology, University of Toledo Health Sciences Campus, Toledo, OH, USA

Andrew J Lutz Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA

Leela L Paris Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA

Massimiliano Veroux Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy; Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy

Simon C Robson Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Michael A Rees Department of Urology, University of Toledo Health Sciences Campus, Toledo, OH, USA; Department of Urology, University of Toledo Health Sciences Campus, Toledo, OH, USA

David Ayares Revivicor, Inc., Blacksburg, VA, USA; Revivicor, Inc., Blacksburg, VA, USA

Bruno Gridelli Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy; Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy

A Joseph Tector Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA; Department of Surgery, Transplant Institute, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA

David KC Cooper Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [email protected]

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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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Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

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Immunobiology of liver xenotransplantation

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Immunobiology of liver xenotransplantation

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