Skip to main content

Xenotransplantation

  • Chapter
  • 297 Accesses

Abstract

An organism consisting of two or more organs of different genetic composition is an ancient concept. Greek, Indian, and Chinese mythologies provide abundant examples of mythical composite creatures with fantastic properties: the Greek Chimera, with three heads (lion, goat, and snake) and a body comprising a lion in the front, a goat in the rear, and snake for a tail; the Indian Ganesh, with the head of an elephant and a body of a man; and the Chinese Phoenix, which is a bird with the neck of a snake, the back of a tortoise, and the tail of a fish. By those standards, the goals of modern xenotransplantation are far less fanciful.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   349.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Evans, R. (1992). Need, demand, and supply in kidney transplantation: A review of the data, an examination of the issues, and projections through the year 2000.Semin. Nephrol.12, 234–255.

    PubMed  CAS  Google Scholar 

  2. Stevenson, L., R. Kormos, R. Bourge, A. Gelijns, B. Griffith, R. Hershbergeret al.(2001). Mechanical cardiac support 2000: current applications and future trial design.J. Am. Coll. Cardiol.37, 340–370.

    Article  PubMed  CAS  Google Scholar 

  3. Kjaergard, L.L., J. Liu, B. Als-Nielsen, and C. Gluud (2003). Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: A systematic reviewJAMA289 217–222.

    Article  PubMed  Google Scholar 

  4. White, S.A. and M.L. Nicholson (1999). Xenotransplantation.Br. J. Surg.199, 1499–1514.

    Article  Google Scholar 

  5. Reemtsma, K., B. McCracken, J. Schlegel, M. Pearl, C. Pearce, C. DeWillet al.(1964). Renal heterotransplantation from baboon to man.Ann. Surg.160, 384–408.

    Article  PubMed  CAS  Google Scholar 

  6. Starzl, T., J. Fung, A. Tzakis, S. Todo, A. Demetris, I. Marinoet al.(1993). Baboon-to-human liver transplantation.Lancet341, 65–71.

    Article  PubMed  CAS  Google Scholar 

  7. Dorling, A., K. Riesbeck, A. Warrens, and R. Lechler (1997). Clinical xenotransplantation of solid organs.Lancet349 867–871.

    Article  PubMed  CAS  Google Scholar 

  8. Caine, R. (1970). Organ transplantation between widely disparate species.Transplant. Proc.2 550–553.

    Google Scholar 

  9. Cascalho, M. and J.L. Platt (2001). The immunological barrier to xenotransplantation.Immunity14 437–446.

    Article  PubMed  CAS  Google Scholar 

  10. JiH.K. Ohmura, U. Mahmood, D.M. Lee, F.M. Hofhuis, S.A. Boackle et al. (2002). Arthritis critically dependent on innate immune system playersImmunity16 157–168.

    Article  PubMed  Google Scholar 

  11. Pangburn, M. (2000). Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complementImmunopharmacology49 149–157.

    Article  PubMed  CAS  Google Scholar 

  12. Good, A., D. Cooper, A. Malcolm, R. Ippolito, E. Koren, F. Neethinget al.(1992). Identification of carbohydrate structures that bind human antiporcine antibodies: Implication for discordant xenografting in humansTransplant. Proc42 559.

    Google Scholar 

  13. Galili, U. (1993). Interaction of the natural anti-Gal antibody with a-galactosyl epitopes: A major obstacle for xenotransplantation in humansImmunol. Today14 480–482.

    Article  PubMed  CAS  Google Scholar 

  14. Galili, U. (1993). Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibodySpringer Semin. Immunopathol15 155–171.

    Google Scholar 

  15. Teranishi, K., R. Manez, M. Awwad, and D. Cooper (2002). Anti-Gal alpha 1–3Gal IgM and IgG antibody levels in sera of humans and old world non-human primatesXenotransplantation9 148–154.

    Article  PubMed  Google Scholar 

  16. Buonomano, R., C. Tinguely, R. Rieben, P. Mohacsi, and U. Nydegger (1999). Quantitation and characterization of anti-Galalphal-3Gal antibodies in sera of 200 healthy personsXenotransplantation6 173–180.

    Article  PubMed  CAS  Google Scholar 

  17. Galili, U., F. Anaraki, A. Thall, C. Hill-Black, and M. Radic (1993). One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody.Blood82, 2485–2493.

    PubMed  CAS  Google Scholar 

  18. Galili, U., R. Mandrell, R. Hamandeh, S.B. Shohet, and J. Griffis (1988). Interaction between human natural anti-a-galactosyl immunoglobulin G and bacteria of the human floraInfect. Immun56 1730.

    PubMed  CAS  Google Scholar 

  19. Yu, P.B. W. Parker, M.L. Everett, I.J. Fox, and J.L. Platt (1999). Immunochemical properties of anti-Gal alpha 1,3Gal antibodies after sensitization with xenogeneic tissuesJ. Clin. Immunol19 116–126.

    Article  PubMed  CAS  Google Scholar 

  20. Romo, G., J. Dong, A. Schade, E. Gardiner, G. Kansas, C. Liet al.(1999). The glycoprotein lb-IX-V complex is a platelet counterreceptor for P-selectin.J. Exp. Med.190, 803–814.

    Article  PubMed  CAS  Google Scholar 

  21. Kobayashi, T., S. Taniguchi, Y. Ye, M. Niekrasz, S. Kosanke, F. Neethlinget al.(1996). Delayed xenograft rejection in C3-depleted discordant (pig-to-baboon) cardiac xenografts treated with cobra venom factor.Transplant. Proc.28, 560.

    PubMed  CAS  Google Scholar 

  22. Kirschfink, M. (2001). Targeting complement in therapy.Immunol. Rev.180, 177–189.

    Article  PubMed  CAS  Google Scholar 

  23. Fodor, W., S. Rollins, E. Guilmette, E. Setter, and S. Squinto (1995). A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complexJ. Immunol. 1554135–4138

    PubMed  CAS  Google Scholar 

  24. Wang, H., S.A. Rollins, Z. Gao, B. Garcia, Z. Zhang, J. Xinget al.(1999). Complement inhibition with an anti-05 monoclonal antibody prevents hyperacute rejection in a xenograft heart transplantation model.Transplantation68, 1643–1651.

    Article  PubMed  CAS  Google Scholar 

  25. Fiane, A., T. Mollnes, V. Videm, T. Hovig, K. Hogasen, O. Mellbyeet al.(1999). Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts.Xenotransplantation6, 52–65.

    Article  PubMed  CAS  Google Scholar 

  26. Cozzi, E., F. Bhatti, M. Schmoeckel, G. Chavez, K.G. Smith, A. Zaidiet al.(2000). Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.Transplantation70, 15–21.

    PubMed  CAS  Google Scholar 

  27. Byrne, G.W., K.R. McCurry, M.J. Martin, S.M. McClellan, J.L. Platt, and J.S. Logan (1997). Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage.Transplantation63, 149–155.

    Article  PubMed  CAS  Google Scholar 

  28. McCurry, K., D. Kooyman, C. Alvarado, A. Cotterell, A. Martin, J. Loganet al.(1995). Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injuryNat. Med. 1423–427

    Article  PubMed  CAS  Google Scholar 

  29. Zhou, C., E. McInnes, N. Parsons, G. Langford, R. Lancaster, A. Richardset al.(2002). Production and characterization of a pig line transgenic for human membrane cofactor protein.Xenotransplantation9, 183–190.

    Article  PubMed  Google Scholar 

  30. Diamond, L.G., C.M. Quinn, M.J. Martin, J.L. Lawson, J.L. Platt, and J.S. Logan (2001). A human CD46 trans-genic pig model system for the study of discordant xenotransplantation.Transplantation71, 132–142.

    Article  PubMed  CAS  Google Scholar 

  31. Lin, S.S. and J.L. Platt (1996). Immunologic barriers to xenotransplantation.J. Heart Lung Transplant.15,547–555.

    PubMed  CAS  Google Scholar 

  32. Lin, S., B. Weidner, G. Byrne, L. Diamond, J. Lawson, C. Hoopeset al.(1998). The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplantsJ. Clin. Invest. 1011745–1756

    Article  PubMed  CAS  Google Scholar 

  33. Lin, S.S., M.J. Hanaway, G.V. Gonzalez-Stawinski, C.L. Lau, W. Parker, R.D. Daviset al.(2000). The role of anti-Gal 1al-3Gal antibodies in acute vascular rejection and accommodation of xenografts.Transplantion70, 1667–1674.

    Article  CAS  Google Scholar 

  34. Lin, S.S., D.L. Kooyman, L.J. Daniels, C.W. Daggett, W. Parker, J.H. Lawsonet al.(1997). The role of natural anti-Gal alpha 1–3Gal antibodies in hyperacute rejection of pig-to-baboon cardiac xenotransplants.Transpl. Immunol.5, 212–218.

    Article  PubMed  CAS  Google Scholar 

  35. Taniguchi, S., F.A. Neethling, E.Y. Korchagina, N. Bovin, Y. Ye, T. Kobayashiet al.(1996). In vivo immunoadsorption of antipig antibodies in baboons using a specific Gal(alpha)1–3Gal column.Transplantation62, 1379–1384.

    Article  PubMed  CAS  Google Scholar 

  36. Alwayn, I., M. Basker, L. Buhler, and D. Cooper (1999). The problem of anti-pig antibodies in pig-to-primate xenografting: Current and novel methods of depletion and/or suppression of production of anti-pig antibodies.Xenotransplantation6, 157–168.

    Article  PubMed  CAS  Google Scholar 

  37. Katopodis, A., R. Warner, R. Duthaler, M. Streiff, A. Bruelisauer, O. Kretzet al.(2002). Removal of antiGalalphal,3Gal xenoantibodies with an injectable polymerJ. Clin. Invest. 1101869–1877

    PubMed  CAS  Google Scholar 

  38. Fryer, J., J. Leventhal, A. Dalmasso, S. Chen, P. Simone, J. Goswitzet al.(1995). Beyond hyperacute rejection: Accelerated rejection in a discordant xenograft model by adoptive transfer of specific subsets.Transplantation59, 171–176.

    PubMed  CAS  Google Scholar 

  39. Leventhal, J., A. Matas, L. Sun, S. Reif, R. Bolman, A. Dalmassoet al.(1993). The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model.Transplantation56, 1–8.

    Article  PubMed  CAS  Google Scholar 

  40. Goddard, M., J. Dunning, J. Horsley, C. Atkinson, G. Pino-Chavez, and J. Wallwork (2002). Histopathology of cardiac xenograft rejection in the pig-to-baboon model. J.Heart Lung Transplant.21, 474–484.

    Article  PubMed  Google Scholar 

  41. Kaplon, R.J., R.E. Michler, H. Xu, P.A. Kwiatkowski, N.M. Edwards, and J.L. Platt (1995). Absence of hyper-acute rejection in newborn pig-to-baboon cardiac xenografts.Transplantation59, 1–6.

    Article  PubMed  CAS  Google Scholar 

  42. Holzknecht, Z., K. Kuypers, T. Plummer, J. Williams, M. Bustos, G. Goreset al.(2002). Apoptosis and cellular activation in the pathogenesis of acute vascular rejection.Circ. Res.91, 1135–1141.

    Article  PubMed  CAS  Google Scholar 

  43. Xu, H., B. Naziruddin, D. Yin, J. Shen, J.S. Logan, G.W. Byrneet al.(2003). Functional characteristics of anti-Gal monoclonal antibodies: Correlation between in vitro and in vivo activity.1 Immunol.170, 1531–1539.

    CAS  Google Scholar 

  44. Foreman, K.E., A.A. Vaporciyan, B.K. Bonish, M.L. Jones, K.J. Johnson, M.M. Glovskyet al.(1994). C5a-induced expression of P-selectin in endothelial cells.J. Clin. Invest.94, 1147–1155.

    Article  PubMed  CAS  Google Scholar 

  45. Kozlowski, T., R. Monroy, Y. Xu, R. Glaser, M. Awwad, D. Cooper, and D. Sachs (1998). Anti-Gal (alpha) 1–3Gal antibody response to porcine bone marrow in unmodified baboons and baboons conditioned for tolerance induction.Transplantation66, 176–182.

    Article  PubMed  CAS  Google Scholar 

  46. Galili, U., A. Tibell, B. Samuelsson, L. Rydberg, and C. Groth (1995). Increased anti-Gal activity in diabetic patients transplanted with fetal porcine islet cell clusters.Transplantation59, 1549–1556.

    PubMed  CAS  Google Scholar 

  47. Buhler, L., M. Awwad, M. Basker, S. Gojo, A. Watts, S. Treter (2000). High-dose porcine hematopoietic cell transplantation combined with CD40 ligand blockade in baboons prevents an induced anti-pig humoral response.Transplantation69, 2296–2304.

    Article  PubMed  CAS  Google Scholar 

  48. Diamond, L., G. Byrne, A. Schwarz, T. Davis, D. Adams, and J. Logan (2002). Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha]-3 galactose trisaccharide-polyethylene glycol conjugateTransplantation73 1780–1787.

    Article  PubMed  CAS  Google Scholar 

  49. Teranishi, K., B. Gollackner, L. Buhler, C. Knosalla, L. Correa, J. Downet al.(2002). Depletion of anti-gal antibodies in baboons by intravenous therapy with bovine serum albumin conjugated to gal oligosaccharides.Transplantation73, 129–139.

    Article  PubMed  CAS  Google Scholar 

  50. Thall, A., P. Maly, and J. Lowe (1995). Oocyte Galal,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse.J. Biol. Chem.270, 21437–21440.

    Article  PubMed  CAS  Google Scholar 

  51. Tearle, R., M. Tange, Z. Zannettino, M. Katerelos, T. Shinkel, B. van Denderenet al.(1996). The a1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation.Transplantation61, 13–19.

    Article  PubMed  CAS  Google Scholar 

  52. Campbell, K., J. McWhir, W. Ritchie, and I. Wilmut (1996). Sheep cloned by nuclear transfer from a cultured cell line.Nature380, 64–66.

    Article  PubMed  CAS  Google Scholar 

  53. Polejaeva, I., S. Chen, T. Vaught, R. Page, J. Mullins, S. Ballet al.(2000). Cloned pigs produced by nuclear transfer from adult somatic cells.Nature407, 86–90.

    Article  PubMed  CAS  Google Scholar 

  54. Baguisi, A., E. Behboodi, D. Melican, J. Pollock, M. Destrempes, C. Cammusoet al.(1999). Production of goats by somatic cell nuclear transfer.Nat. Biotechnol.17, 456–461.

    Article  PubMed  CAS  Google Scholar 

  55. Cibelli, J., S. Stice, P. Golueke, J. Kane, J. Jerry, C. Blackwellet al.(1998). Cloned transgenic calves produced from nonquiescent fetal fibroblasts.Science280, 1256–1258.

    Article  PubMed  CAS  Google Scholar 

  56. Wakayama, T., I. Rodriguez, A. Perry, R. Yanagimachi, and P. Mombaerts (1999). Mice cloned from embryonic stem cells.Proc. Natl. Acad. Sci. USA96, 14984–14989.

    Article  PubMed  CAS  Google Scholar 

  57. Onishi, A., M. Iwamoto, T. Akita, S. Mikawa, K. Takeda, T. Awataet al.(2000). Pig cloning by microinjection of fetal fibroblast nuclei.Science289, 1188–1190.

    Article  PubMed  CAS  Google Scholar 

  58. McCreath, K., J. Howcroft, K. Campbell, A. Colman, A. Schnieke, and A. Kind (2000). Production of gene-targeted sheep by nuclear transfer from cultured somatic cells.Nature405, 1066–1069.

    Article  PubMed  CAS  Google Scholar 

  59. Bondioli K., J. Ramsoondar, B. Williams, C. Costa, and W. Fodor (2001). Cloned pigs generated from cultured skin fibroblasts derived from a H-transferase transgenic boar.Mol. Reprod. Dev.60, 189–195.

    Article  PubMed  CAS  Google Scholar 

  60. Dai, Y., T. Vaught, J. Boone, S. Chen, C. Phelps, S. Ballet al.(2002). Targeted disruption of the alphal, 3-galactosyltransferase gene in cloned pigs.Nat. Biotechnol.20, 251–255.

    Article  PubMed  CAS  Google Scholar 

  61. Lai, L., D. Kolber-Simonds, K.W. Park, H.T. Cheong, J.L. Greenstein, G.S. Imet al.(2002). Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning.Science295, 1089–1092.

    Article  PubMed  CAS  Google Scholar 

  62. Phelps, C.J., C. Koike, T.D. Vaught, J. Boone, K.D. Wells, S.-H. Chenet al.(2002). Production of a1,3Galactosyltransferase-deficient pigs.Science299, 411–414.

    Article  PubMed  Google Scholar 

  63. Patience, C., Y. Takeuchi, and R. Weiss (1997). Infection of human cells by an endogenous retrovirus of pigs.Nat. Med.3, 282–286.

    Article  PubMed  CAS  Google Scholar 

  64. Paradis, K., G. Langford, Z. Long, W. Heneine, P. Sandstrom, W. Switzeret al.(1999). Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group.Science285, 1236–1241.

    Article  PubMed  CAS  Google Scholar 

  65. van der Laan, L., C. Lockey, B. Griffeth, E Frasier, C. Wilson, D. Onionset al.(2000). Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice.Nature407, 90–94.

    Article  PubMed  Google Scholar 

  66. Rother, R., W. Fodor, J. Springhorn, C. Birks, E. Setter, M. Sandrinet al.(1995). A novel mechanism of retrovirus inactivation in human serum mediated by anti-alpha-galactosyl natural antibody.J. Exp. Med.182, 1345–1355.

    Article  PubMed  CAS  Google Scholar 

  67. Platt, J.L. (2000). Xenotransplantation. New risks, new gains.Nature27, 29–30.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chong, A.S., Boussy, I.A., Byrne, G.W. (2004). Xenotransplantation. In: Wilkes, D.S., Burlingham, W.J. (eds) Immunobiology of Organ Transplantation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8999-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-8999-4_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4754-5

  • Online ISBN: 978-1-4419-8999-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics