Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation

A. Joseph Tector, Mariana Berho, Jonathan A. Fridell, Antonio DiCarlo, S. Liu, Carl Soderland, Jeffrey S. Barkun, Peter Metrakos, Jean I. Tchervenkov

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The pathophysiological state of rejection in liver xeno-transplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xeno-reactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.

Original languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalLiver Transplantation
Volume7
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Heterologous Transplantation
Liver Failure
Heterografts
Swine
Liver
Serum
Healthy Volunteers
Perfusion
Complement C3b
Complement Membrane Attack Complex
Complement Activation
Wounds and Injuries
Liver Transplantation
Endothelium
Immunoglobulin M
Hepatocytes
Endothelial Cells
Animal Models

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Tector, A. J., Berho, M., Fridell, J. A., DiCarlo, A., Liu, S., Soderland, C., ... Tchervenkov, J. I. (2001). Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation. Liver Transplantation, 7(2), 82-89. https://doi.org/10.1053/jlts.2001.21281

Rejection of pig liver xenografts in patients with liver failure : Implications for xenotransplantation. / Tector, A. Joseph; Berho, Mariana; Fridell, Jonathan A.; DiCarlo, Antonio; Liu, S.; Soderland, Carl; Barkun, Jeffrey S.; Metrakos, Peter; Tchervenkov, Jean I.

In: Liver Transplantation, Vol. 7, No. 2, 2001, p. 82-89.

Research output: Contribution to journalArticle

Tector, AJ, Berho, M, Fridell, JA, DiCarlo, A, Liu, S, Soderland, C, Barkun, JS, Metrakos, P & Tchervenkov, JI 2001, 'Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation', Liver Transplantation, vol. 7, no. 2, pp. 82-89. https://doi.org/10.1053/jlts.2001.21281
Tector, A. Joseph ; Berho, Mariana ; Fridell, Jonathan A. ; DiCarlo, Antonio ; Liu, S. ; Soderland, Carl ; Barkun, Jeffrey S. ; Metrakos, Peter ; Tchervenkov, Jean I. / Rejection of pig liver xenografts in patients with liver failure : Implications for xenotransplantation. In: Liver Transplantation. 2001 ; Vol. 7, No. 2. pp. 82-89.
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