Liver Xenotransplantation: Clinical Experience and Future Considerations

  • D. V. Cramer
  • L. Sher
  • L. Makowka


The use of xenografts in liver transplantation offers several distinct advantages for the treatment of patients with end-stage liver disease and fulminant liver failure. The first is the availabihty of a predictable and ready supply of donor organs. At the present time the most critical element restricting the widespread apphcation of liver transplantation as a therapeutic modality is the shortage of human donor organs. It has been estimated that approximately 20%–25% of patients awaiting liver transplantation die due to lack of an appropriate donor organ. The limited supply of donor organs also has the effect of limiting the size of the potential pool of recipients that may benefit from the procedure. An increased supply of suitable organs will result in a large increase in the number of transplants performed.


Donor Organ Biliary Atresia Natural Antibody Acute Hepatic Failure Hyperacute Rejection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dubernard, J.M., Bonneau, M., Latour, M. Heterografts in Primates. Simep Editions, Villeurbanne, France, 1974.Google Scholar
  2. 2.
    Auchincloss, H. Jr. Xenogeneic transplantation. A review. Transplantation. 46,1, 1988.PubMedCrossRefGoogle Scholar
  3. 3.
    Norman, J.C., Saravis, C.A., Brown, M.E., McDermott, W.V. Jr. Immunochemical observahons in chnical heterologous (xenogeneic) hver perfusions. Surgery. 60,179, 1966.Google Scholar
  4. 4.
    Hickman, R., Saunders, S.J., Goodwin, N.E., Terblanche, J. Perfusion of the isolated pig hver with human blood. J. Surg. Res. 11,519, 1971.PubMedCrossRefGoogle Scholar
  5. 5.
    Abouna, G.M., Serrou, B., Boehmig, H.G., Amemiya, H., Marineau, G. Long-term support by intermittent mulh-species liver perfusions. Lancet 2,391, 1970.PubMedCrossRefGoogle Scholar
  6. 6.
    Starzl T.E., Marchioro, T.L. Faris. T.D., McCardle. M.J. Iwasaki, Y. Avenues of future research in homotransplantation of the liver. Amer. J. Surg. 112,391, 1966.PubMedCrossRefGoogle Scholar
  7. 7.
    Starzl, T.E. Experience in Hepatic Transplantation. Saunders, Philadelphia, 1969, p. 408.Google Scholar
  8. 8.
    Giles, G.R., Boehmig, H.J., Amemiya, H., Halgrimson, C.G., Starzl, T.E. Chnical heterotransplantation of the liver. Transplant. Proc. 2,506, 1970.PubMedGoogle Scholar
  9. 9.
    Starzl, T.E., Ishikawa, M., Putman, C.W., Porter, K.A., Picache, R., Husberg, B.S. Halgrimson, C.G., Schröter, G. Progress in and deterrents to orthotopic liver transplantation, with special reference to survival, resistance to hyperacute rejection, and bihary duct reconstruction. Transplant. Proc. 6,129, 1974.PubMedGoogle Scholar
  10. 10.
    Porter, K.A. Pathology of the orthotopic homograft and heterograft. In: Experience in Hepatic Transplantation. T.E. Starzl (ed.), W.B. Saunders, Philadelphia. 1969, p. 422.Google Scholar
  11. 11.
    Makowka, L., Chapman, F.A., Cramer, D.V., Quian, S.G., Sun, H., Starzl, T.E. Platelet- activating factor and hyperacute rejection. The effect of a platelet-activating factor antagonist, SRI 63–441, on rejection of xenografts and allografts in sensitized hosts. Transplantation. 50,359, 1990.PubMedCrossRefGoogle Scholar
  12. 12.
    Miyagawa, S., Hirose, H., Shirakura, R., Naka, Y., Nakata, S., Kawashima, V., Seya, T., Matsumoto, M., Venaka, A., Kitamura, H. The mechanism of discordant xenograft rejection. Transplantation. 46,825, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Starzl, T.E., Demetris, A.J. Liver Transplantation: a 31-year Perspective. Year Book Medical Publ., Inc., Chicago, 1990.Google Scholar
  14. 14.
    Monden, M., Valdivia, L.A., Gotoh, M., Hasuike, Y., Kubota, N., Kanai, T., Okamura, J., Mori, T. Hamster-to-rat orthotopic liver xenografts. Transplantation. 43,745, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Calne, R.Y. Organ transplantation between widely disparate species. Transplant. Proc. 2,550, 1970.PubMedGoogle Scholar
  16. 16.
    Reemtsma, K. Renal heterotransplantation from non-human primates to man. Ann. N.Y.Acad. Sci. 162,412, 1969.PubMedCrossRefGoogle Scholar
  17. 17.
    Eiseman, B., Lam, D.S., Raffucci, F. Heterologous hver perfusion in treatment of hepatic failure. Surg. 162,329, 1965.Google Scholar
  18. 18.
    Ham, J.M., Piróla, R.C., Davidson, R.M., Ayrrow, S., Elmsliz, R.G. Pig liver perfusion for the treatment of acute hepatic coma. Surg. Gynecol. Obstet. 127,453, 1968.Google Scholar
  19. 19.
    Shons, A.R., Najarian, J.S. Xenograft rejection mechanisms in man. Trans. Am. Soc. Artif. Intern. Organs. 20,562, 1973.Google Scholar
  20. 20.
    Edwards, N., Ott, G., Berger, C., He, X.,Teppler, I., Copey, L., Smith, C., Reemtsma, K., Rose, E. Incidence of preformed antibodies against potential xeno-donors in human serum. Transplantation. 49,1022, 1990.Google Scholar
  21. 21.
    Platt, J.L., Vercellotti, G.M., Lindman, B.J., Oegema, T.R. Jr., Bach, F.H., Dalmasso, A.P. Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection. J. Exp. Med. 171,1363, 1990.PubMedCrossRefGoogle Scholar
  22. 22.
    Otte, K.E., Andersen, N., Jorgensen, K.A., Kristensen, T., Barfort, P., Starklint, H., Larsen, S., Kemp, E. Xenoperfusion of pig kidney with human AB or O blood. Transplant. Proc. 22,1091, 1990.PubMedGoogle Scholar
  23. 23.
    Calne, R.Y., White, H.J.O., Herbertson, B.M., Millard, P.R., Davis, D.R., Salaman, J.R., Samuel, J.R. Pig-to-baboon liver xenografts. Lancet. 1,1176, 1968.PubMedCrossRefGoogle Scholar
  24. 24.
    Calne, R.Y., Davis, D.R., Pena, J.R., Balner, H., De Vries, M., Herbertson, B.M., Millard, P.R., Joysey, V.C., Seaman, M.J., Samuel, J.R., Stibbe, J., Westbroek, D.L. Hepatic allografts and xenografts in primates. Lancet. 1,103, 1970.PubMedCrossRefGoogle Scholar
  25. 25.
    Knoop, M., Steffen, R., Orlof, M.S., Cramer, D.V. Overview: The importance of hepatic artery reconstitution in orthotopic hver transplantation. Submitted for publication.Google Scholar
  26. 26.
    Gordon, R.D., Iwatsuki, S., Esquivel, C.O., Tzakis, A., Todo, S., Starzl, T.E. Liver transplantation across ABO blood groups. Surgery. 100,342, 1986.PubMedGoogle Scholar
  27. 27.
    Gordon, R.D., Fung, J.J., Markus, B., Fox, I., Iwatsuki, S., Esquivel, C.O., Tzakis, A., Todo, S., Starzl, T.E. The antibody crossmatch in hver transplantation. Surgery. 100,705, 1986.PubMedGoogle Scholar
  28. 28.
    Kamada, N., Davies, H., Roser, B. Reversal of transplantation immunity by liver grafting. Nature. 292,840, 1981.PubMedCrossRefGoogle Scholar
  29. 29.
    Knechtle, S.J., Kolbeck, P.C., Tsuchimoto, S., Coundouriotis, A., Sanfilippo, F., Bollinger, R.R. Hepatic transplantation into sensitized recipients. Transplantation. 43,8, 1987.PubMedCrossRefGoogle Scholar
  30. 30.
    Demetris, A.J., Jaffe, R., Tzakis, A., Ramsey, G., Todo, S., Belle, S., Esquivel, C., Shapiro, R., Markus, B., Mroczek, E. Antibody mediated rejection of human orthotopic hver allografts: a study of hver transplantation across ABO blood group barriers. Am. J. Pathol. 132,489, 1988.PubMedGoogle Scholar
  31. 31.
    Merion, R.M., Colletti, L.M. Hyperacute rejection in porcine hver transplantation. L Chnical characteristics, histopathology, and disappearance of donor-specific lymphocytotoxic antibody from serum. Transplantation. 49,861, 1990.PubMedCrossRefGoogle Scholar
  32. 32.
    Makowka, L.M., Chapman, P., Cramer, D., Sher, L., Podesta, L., Howard, T., Starzl, T.E. The role of inflammatory reactions in xenotransplantation. In: Xenograft 25. Hardy, M.A. (ed.), Elsevier; Amsterdam, New York, Oxford, 1989, p. 159.Google Scholar
  33. 33.
    Valdivia, L.A., Monden, M., Gotoh, M., Nakano, Y., Tono, T., Mori, T. Evidence that deoxyspergualin prevents sensitization and first-set cardiac xenograft rejection in rats by suppression of antibody formation. Transplantation. 50,132, 1990.PubMedCrossRefGoogle Scholar
  34. 34.
    Knechtle, S.J., Halperin, E.C., Saad, T., Bohinger, R.R. Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine. J. Heart Transplant. 5, 254, 1986.PubMedGoogle Scholar
  35. 35.
    Slavin, S., Strober, S., Fuks, Z., Kaplan, H.S. Induction of specific transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts. J. Exp. Med. 146,34, 1977.PubMedCrossRefGoogle Scholar
  36. 36.
    Ilstad, S.M., Sachs, D.H. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of skin ahografts or xenografts. Nature. 307, 168, 1984.CrossRefGoogle Scholar
  37. 37.
    Zijlstra, M., Bix, M., Simister, N.E., Loring, J.M., Raulet, D.H., Jaenisch, R. P2-micro- globulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 34,743, 1990.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • D. V. Cramer
  • L. Sher
  • L. Makowka

There are no affiliations available

Personalised recommendations