Chapter 1 : A Primer on Xenotransplantation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

A Primer on Xenotransplantation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap01-2.gif


No area of medicine stimulates as much excitement or as much controversy as transplantation. The rationale for xenotransplantation is the shortage of human organs and tissues. For several reasons, however, most in the field of xenotransplantation have abandoned the use of nonhuman primates. Therefore, instead of using primates, most in the field of transplantation focus on the use of pigs or other non-primate species. If opportunities offered by xenotransplantation are great, the hurdles, at present, appear equally so. These hurdles include (i) the immune response of the host against the graft leading to rejection of the graft, (ii) the inherent physiologic limitations of the animal tissue or organ in a human system or induced disruption of the normal functions of the recipient, and (iii) the possibility of transferring infectious agents from the transplant to the recipient and, potentially, more broadly to the general population. This chapter focuses on the hurdles to transplanting porcine organs and cells into humans. The past few years have brought significant progress in defining the hurdles to xenotransplantation and progress in overcoming the immunologic and physiologic hurdles in this field.

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1

Key Concept Ranking

Immune Systems
Complement System
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

The immunological responses to xenotransplantation of various tissue types. Xenografts of free tissues such as pancreatic islets or isolated cells such as bone marrow cells are subject to early failure due to primary non-function, failure to neovascularize, or molecular incompatibilities and subsequent cell-mediated rejection. A porcine organ transplanted into a human would be subject to one or more of the immunological reactions shown here. Transplantation into an untreated recipient would give rise to hyperacute rejection. If hyperacute rejection is avoided, for example, by the inhibition of complement, the graft is subjected to acute vascular rejection. If anti-donor antibodies are depleted from the recipient, the graft may undergo accommodation, a condition in which acute vascular rejection does not occur despite the presence of anti-donor antibodies in the circulation of the recipient. If acute vascular rejection is avoided, the graft will undergo cell-mediated rejection or chronic rejection.

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Possible ways in which Galαl-3Gal expression could be decreased by genetic engineering. Synthesis of Gal1-3Gal is catalyzed by 1,3-galactosyltransferase (GT); the biosynthetic pathway is shown by dashed arrows. This enzyme adds galactose residues at the termini of oligosaccharide chains. Four possible approaches to preventing the synthesis of the sugar are shown by normal arrows. First, the expression of antisense RNA or a ribozyme might disrupt the structure or function of the GT mRNA. Second, introduction of a gene for an inhibitory ligand for GT, such as an appropriate Fv (an antibody-like molecule) or an aptamer (a small oligonucleotide inhibitor), might inhibit the function of the enzyme. Third, overexpression of another glycosyl transferase, such as H transferase, which adds fucose residues, might compete for the subterminal residues on oligosaccharide chains. This has been achieved in rats by the overexpression of a human H transferase, resulting in the addition of fucose rather than Gal1-3Ga1 to oligosaccharide side chains ( ). Fourth, expression of a glycosidase, such as a-galactosidase, might lead to cleavage of the antigenic saccharide chains. Reprinted by permission from 392(Suppl.):l 1-17, 1998, Macmillan Magazines Ltd.

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Akhter, S. A.,, C. A. Skaer,, A. P. Kypson,, P. H. McDonald,, K. C. Peppel,, D. D. Glower,, R. J. Lefkowitz,, and W. J. Koch. 1997. Restoration of β-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer. Proc. Nat. Acad. Sci. USA 94:1210012105.
2. Alexandre, G. P. J.,, P. Gianello,, D. Latinne,, M. Carlier,, A. Dewaele,, L. Van Obbergh,, M. Moriau,, E. Marbaix,, J. L. Lambotte,, L. Lambotte,, and J. P. Squifflet,. 1989. Plasmapheresis and splenectomy in experimental renal xenotransplantation, p. 259266. In M. A. Hardy (ed.), Xenograft 25. Elsevier Science Publishers, New York, N.Y.
3. Alvarado, C. G.,, A. H. Cotterell,, K. R. McCurry,, B. H. Collins,, J. C. Magee,, J. Berthold,, J. S. Logan,, and J. L. Platt. 1995. Variation in the level of xenoantigen expression in porcine organs. Transplantation 59:15891596.
4.Anonymous. November 14,1911. Dr. Hammond gives patient new kidney. The New York Times, New York, N.Y.
5.Anonymous. November 15, 1911. A new surgical feat. The New York Times, New York, N.Y.
6. Atkinson, J. P.,, T. J. Oglesby,, D. White,, E. A. Adams,, and M. K. Liszewski. 1991. Separation of self from non-self in the complement system: a role for membrane cofactor protein and decay accelerating factor. Clin. Exp. Immunol. 86(Supp. l):2730.
7. Bach, F. H.,, C. Ferran,, P. Hechenleitner,, W. Mark,, N. Koyamada,, T. Miyatake,, H. Winkler,, A. Badrichani,, D. Cardinas,, and W. H. Hancock. 1997. Accommodation of vascularized xenografts: expression of “protective genes” by donor endothelial cells in a host Th2 cytokine environment. Nature Med. 3:196204.
8. Bach, F. H.,, H. Winkler,, C. Ferran,, W. W. Hancock,, and S. C. Robson. 1996. Delayed xenograft rejection. Immunol. Today 17:379384.
9. Blakely, M. L.,, W. J. Van Der Werf,, M. C. Berndt,, A. P. Dalmasso,, F. H. Bach,, and W. W. Hancock. 1994. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 58:10591066.
10. Blau, H. M.,, and M. L. Springer. 1995. Muscle-mediated gene therapy. N. Engl. J. Med. 333:15541556.
11. Brauer, R. B.,, W. M. Baldwin III,, M. R. Daha,, S. K. Pruitt,, and F. Sanfilippo. 1993. Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts. J. Immunol. 151:72407248.
12. Brent, L. 1997. Clinical aspects and immunosuppression, p. 306343. In A History of Transplantation Immunology. Academic Press, San Diego, Calif.
13. Bustos, M.,, and J. L. Platt. 1997. Platelet-endothelial cell interactions in a xenograft model. Transplant. Proc. 29:886.
14. Bustos, M.,, S. Saadi,, and J. L. Platt. Platelet-mediated activation of endothelial cells: implications for the pathogenesis of transplant rejection. Submitted.
15. 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. Transplantation 63:149155.
16. Calne, R. Y.,, D. R. Davis,, J. R. Pena,, H. Balner,, M. De Vries,, B. M. Herbertson,, V. C. Joysey,, P. R. Millard,, M. J. Seaman,, J. R. Samuel,, J. Stibbe,, and D. L. Westbroek. 1970. Hepatic allografts and xenografts in primates. Lancet 1:103106.
17. Calne, R. Y.,, H. J. O. White,, B. M. Herbertson,, P. R. Millard,, D. R. Davis,, J. R. Salaman,, and J. R. Samuel. 1968. Pig-to-baboon liver xenografts. Lancet 1:11761178.
18. Carrel, A. 1914. The transplantation of organs. N.Y. J. Med. 99:839840.
19. Chart, R. S.,, B. H. Collins,, J. C. Magee,, A. D. Kirk,, R. C. Harland,, R. L. McCann,, J. L. Platt,, and W. C. Meyers. 1994. Treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N. Engl. J. Med. 331:234237.
20. Chopek, M. W.,, R. L. Simmons,, and J. L. Platt. 1987. ABO-incompatible renal transplantation: initial immunopathologic evaluation. Transplant. Proc. 19:45534557.
21. Collins, B. H.,, W. Parker,, and J. L. Platt. 1994. Characterization of porcine endothelial cell determinants recognized by human natural antibodies. Xenotransplantation 1:3646.
22. Cotterell, A. H.,, B. H. Collins,, W. Parker,, R. C. Harland,, and J. L. Platt. 1995. The humoral immune response in humans following cross-perfusion of porcine organs. Transplantation 60:861868.
23. Cozzi, E.,, and D. J. G. White. 1995. The generation of transgenic pigs as potential organ donors for humans. Nature Med. 1:964966.
24. Cozzi, E.,, N. Yannoutsos,, G. A. Langford,, G. Pino-Chavez,, J. Wallwork,, and D. J. G. White,. 1997. Effect of transgenic expression of human decay-accelerating factor on the inhibition of hyperacute rejection of pig organs, p. 665682. In D. K. C. Cooper,, E. Kemp,, J. L. Platt,, and D. J. G. White (ed.), Xenotransplantation: The Transplantation of Organs and Tissues Between Species, 2nd ed. Springer, Berlin, Germany.
25. Daggett, C. W.,, M. Yeatman,, A. J. Lodge,, E. P. Chen,, C. Gullotto,, M. M. Frank,, J. L. Platt,, and R. D. Davis. 1998. Total respiratory support from swine lungs in primate recipients. J. Thome. Cardiovasc. Surg. 115:1927.
26. Dalmasso, A. P.,, G. M. Vercellotti,, J. L. Platt,, and F. H. Bach. 1991. Inhibition of complement-mediated endothelial cell cytotoxicity by decay accelerating factor: potential for prevention of xenograft hyperacute rejection. Transplantation 52:530533.
27. Deacon, T.,, J. Schumacher,, J. Dinsmore,, C. Thomas,, P. Palmer,, S. Kott,, A. Edge,, D. Penney,, S. Kassissieh,, P. Dempsey,, and O. Isacson. 1997. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson’s disease. Nature Med. 3:350353.
28. Diamond, L. E.,, K. R. McCurry,, E. R. Oldham,, S. B. McClellan,, M. J. Martin,, J. L. Platt,, and J. S. Logan. 1996. Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium. Transplantation 61:12411249.
29. Edwards, J. 1981. Complement activation by xenogeneic red blood cells. Transplantation 31:226227.
30. Evans, R. W.,, C. E. Orians,, and N. L. Ascher. 1992. The potential supply of organ donors: an assessment of the efficiency of organ procurement efforts in the United States. J. Am. Med. Assoc. 267:239246.
31. Exner, B. G.,, M. Neipp,, and S. T. Ildstad. 1997. Baboon bone marrow transplantation in humans: application of cross-species disease resistance. World J. Surg. 21:962967.
32. Galili, U.,, M. R. Clark,, S. B. Shohet,, J. Buehler,, and B. A. Macher. 1987. Evolutionary relationship between the natural anti-Gal antibody and the Galα1-3Gal epitope in primates. Proc. Nat. Acad. Sci. USA 84:13691373.
33. Galili, U.,, I. Flechner,, A. Knyszynski,, D. Danon,, and E. A. Rachmilewitz. 1986. The natural anti-α-galactosyl IgG on human normal senescent red blood cells. B. J. Haematol. 62:317324.
34. Galili, U.,, R. E. Mandrell,, R. A. Hamadeh,, S. B. Shohet,, and J. M. Griffiss. 1988. Interaction between human natural anti-α-galactosyl immunoglobulin G and bacteria of the human flora. Infect. Immun. 56:17301737.
35. Geller, R. L.,, P. Rubinstein,, and J. L. Platt. 1994. Variation in expression of porcine xenogeneic antigens. Transplantation 58:272277.
36. Geller, R. L.,, M. Turman,, F. H. Bach,, and J. L. Platt. 1992. Deposition of polyreactive antibodies in xenograft rejection: detection using anti-idiotype monoclonal antibodies. Transplant. Proc. 24:595.
37. Good, A. H.,, D. K. C. Cooper,, A. J. Malcolm,, R. M. Ippolito,, E. Koren,, F. A. Neethling,, Y. Ye,, N. Zuhdi,, and L. R. Lamontagne. 1992. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant. Proc. 24:559562.
38. Gritsch, H. A.,, R. M. Glaser,, D. W. Emery,, L. A. Lee,, C. V. Smith,, T. Sablinski,, J. S. Arn,, D. H. Sachs,, and M. Sykes. 1994. The importance of nonimmune factors in reconstitution by discordant xenogeneic hematopoietic cells. Transplantation 57:906917.
39. Groth, C. G.,, O. Korsgren,, A. Tibell,, J. Tollemar,, E. Moller,, J. Bolinder,, J. Ostman,, F. P. Reinholt,, C. Hellerstrom,, and A. Andersson. 1994. Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344:14021404.
40. Guthrie, C. C. 1912. Blood-Vessel Surgery and Its Applications. Longmans, Green & Co., New York, N.Y.
41. Heneine, W.,, A. Tibell,, W. M. Switzer,, P. Sandstrom,, G. V. Rosales,, A. Mathews,, O. Korsgren,, L. E. Chapman,, T. M. Folks,, and C. G. Groth. 1998. No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 352:695699.
42. Holzknecht, Z. E.,, S. Coombes,, B. A. Blocher,, T. B. Plummer,, M. Bustos,, C. L. Lau,, R. D. Davis,, and J. L. Platt. Immune complex formation after xenotransplantation. Submitted.
43. Holzknecht, Z. E.,, S. Coombes,, B. A. Blocher,, T. B. Plummer,, M. Bustos,, C. L. Lau,, R. D. Davis,, and J. L. Platt. Evidence of immunocomplex formation in pulmonary xenografts. Transplant. Proc. In press.
44. Holzknecht, Z. E.,, and J. L. Platt. 1995. Identification of porcine endothelial cell membrane antigens recognized by human xenoreactive antibodies. J. Immunol. 154:45654575.
45. Inverardi, L.,, B. Clissi,, A. L. Stolzer,, J. R. Bender,, and R. Pardi. 1996. Overlapping recognition of xenogeneic carbohydrate ligands by human natural killer lymphocytes and natural antibodies. Transplant. Proc. 28:552.
46. Inverardi, L.,, M. Samaja,, R. Motterlini,, F. Mangili,, J. R. Bender,, and R. Pardi. 1992. Early recognition of a discordant xenogeneic organ by human circulating lymphocytes. J. Immunol. 149:14161423.
47. Jaboulay, M. 1906. De reins au pli du coude par soutures arterielles et veineuses. Lyon Med. 107:575577.
48. Jooste, S. V.,, R. B. Colvin,, and H. J. Winn. 1981. The vascular bed as the primary target in the destruction of skin grafts by antiserum. J. Exp. Med. 154:13321341.
49. Kaplon, R. J.,, R. E. Michler,, H. Xu,, P. A. Kwiatkowski,, N. M. Edwards,, and J. L. Platt. 1994. Absence of hyperacute rejection in newborn pig-to-baboon cardiac xenografts. Transplantation 59:16.
50. Kaplon, R. J.,, J. L. Platt,, P. A. Kwiatkowski,, N. M. Edwards,, H. Xu,, A. S. Shah,, and R. E. Michler. 1995. Absence of hyperacute rejection in pig-to-primate orthotopic pulmonary xenografts. Transplantation 59:410416.
51. Kaufman, D. B.,, J. L. Platt,, E. L. Rabe,, P. G. Stock,, and D. E. R. Sutherland. 1990. The immunological basis of islet allograft primary non-function. J. Exp. Med. 172:291302.
52. Kypson, A. P.,, K. Peppel,, S. A. Akhter,, R. E. Lilly,, D. D. Glower,, R. J. Lefkowitz,, and W. J. Koch. 1998. Ex vivo adenoviral-mediated gene transfer to the adult rat heart. J. Thorac. Cardiovasc. Surg. 115:623630.
53. Lawson, J. H.,, L. Daniels,, and J. L. Platt. 1997. The evaluation of thrombomodulin activity in porcine to human xenotransplantation. Transplant. Proc. 29:884885.
54. Lawson, J. H.,, and J. L. Platt. 1996. Molecular barriers to xenotransplantation. Transplantation 62:303310.
55. Leventhal, J. R.,, A. J. Matas,, L. H. Sun,, S. Reif,, R. M. Bolman,, A. P. Dalmasso,, and J. L. Platt. 1993. The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model. Transplantation 56:18.
56. Leventhal, J. R.,, P. Sakiyalak,, J. Witson,, P. Simone,, A. J. Matas,, R. M. Bolman,, and A. P. Dalmasso. 1994. The synergistic effect of combined antibody and complement depletion on discordant cardiac xenograft survival in nonhuman primates. Transplantation 57:974978.
57. Li, H.,, C. Ricordi,, A. J. Demetris,, C. L. Kaufman,, C. Korbanic,, M. L. Hronakes,, and S. T. Ildstad. 1994. Mixed xenogeneic chimerism (mouse+rat*>mouse) to induce donor-specific tolerance to sequential or simultaneous islet xenografts. Transplantation 57:592598.
58. Lin, S. S.,, D. L. Kooyman,, L. J. Daniels,, C. W. Daggett,, W. Parker,, J. H. Lawson,, C. W. Hoopes,, C. Gullotto,, L. Li,, P. Birch,, R. D. Davis,, L. E. Diamond,, J. S. Logan,, and J. L. Platt. 1997. The role of natural anti-Galα1-3Gal antibodies in hyperacute rejection of pig-to-baboon cardiac xenotransplants. Transplant. Immunol. 5:212218.
59. Lin, S. S.,, and J. L. Platt. 1998. Genetic therapies for xenotransplantation. J. Am. Coll. Surg. 186:388396.
60. Lin, S. S.,, B. C. Weidner,, G. W. Byrne,, L. E. Diamond,, J. H. Lawson,, C. W. Hoopes,, L. J. Daniels,, C. W. Daggett,, W. Parker,, R. C. Harland,, R. D. Davis,, R. R. Bollinger,, J. S. Logan,, and J. L. Platt. 1998. The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants. J. Clin. Invest. 101:17451756.
61. Logan, J. S.,, and M. J. Martin. 1994. Transgenic swine as a recombinant production system for human hemoglobin. Meth. Enzymol. 231:435445.
62. Magee, J. C.,, B. H. Collins,, R. C. Harland,, B. J. Lindman,, R. R. Bollinger,, M. M. Frank,, and J. L. Platt. 1995. Immunoglobulin prevents complement mediated hyperacute rejection in swine-to-primate xenotransplantation. J. Clin. Invest. 96:24042412.
63. Malyguine, A. M.,, S. Saadi,, R. A. Holzknecht,, C. R. Parte,, N. Sud,, J. L. Platt,, and J. R. Dawson. 1997. Induction of procoagulant function in porcine endothelial cells by human NK cells. J. Immunol. 159:46594664.
64. Malyguine, A. M.,, S. Saadi,, J. L. Platt,, and J. R. Dawson. 1996. Human natural killer cells induce morphologic changes in porcine endothelial cell monolayers. Transplantation 61:161164.
65. Martin, U.,, V. Kiessig,, J. H. Blusch,, A. Haverich,, K. vonderHelm,, T. Herden,, and G. Steinhoff. 1998. Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 352(9129):692694.
66. McCurry, K. R.,, D. L. Kooyman,, C. G. Alvarado,, A. H. Cotterell,, M. J. Martin,, J. S. Logan,, and J. L. Platt. 1995. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Med. 1:423427.
67. McCurry, K. R.,, W. Parker,, A. H. Cotterell,, B. C. Weidner,, S. S. Lin,, L. J. Daniels,, Z. E. Holzknecht,, G. W. Byrne,, L. E. Diamond,, J. S. Logan,, and J. L. Platt. 1997. Humoral responses in pig-to-baboon cardiac transplantation: implications for the pathogenesis and treatment of acute vascular rejection and for accommodation. Hum. Immunol. 58:91105.
68. Meng, X. J.,, R. H. Pureed,, P. G. Halbur,, J. R. Lehman,, D. M. Webb,, T. S. Tsareva,, J. S. Haynes,, B. J. Thacker,, and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E virus. Proc. Nat. Acad. Sci. USA 94:98609865.
69. Moses, R. D.,, H. J. Winn,, and H. AuchinclossJr.. 1992. Multiple defects in cell surface molecule interactions across species differences are responsible for diminished xenogeneic T cell responses. Transplantation 53:203209.
70. Murray, A. G.,, M. M. Khodadoust,, J. S. Pober,, and A. L. M. Bothwell. 1994. Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. Immunity 1:5763.
71. Ohdan, H.,, Y.-G. Yang,, A. Shimizu,, K. G. Swenson,, and M. Sykes. 1999. Mixed bone marrow chimerism induced without lethal conditioning prevents T cell- and anti-Galα1,3Gal-mediated heart graft rejection. J. Clin. Invest. 104:281290.
72. Paradis, K.,, G. Langford,, Z. Long,, W. Heneine,, P. Sandstrom,, W. M. Switzer,, L. E. Chapman,, C. Lockey,, and D. Onions. 1999. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285:12361241.
73. Parker, W.,, D. Bruno,, Z. E. Holzknecht,, and J. L. Platt. 1994. Xenoreactive natural antibodies: isolation and initial characterization. J. Immunol. 153:37913803.
74. Parker, W.,, K. Lundberg-Swanson,, Z. E. Holzknecht,, J. Lateef,, S. A. Washburn,, S. J. Braedehoeft,, and J. L. Platt 1996. Isohemagglutinins and xenoreactive antibodies are members of a distinct family of natural antibodies. Hum. Immunol. 45:94104.
75. Parker, W.,, S. Saadi,, S. S. Lin,, Z. E. Holzknecht,, M. Bustos,, and J. L. Platt. 1996. Transplantation of discordant xenografts: a challenge revisited. Immunol. Today 17:373378.
76. Parker, W.,, P. B. Yu,, Z. E. Holzknecht,, K. Lundberg-Swanson,, R. H. Buckley,, and J. L. Platt 1997. Specificity and function of “natural” antibodies in immunodeficient subjects: clues to B-cell lineage and development. J. Clin. Immunol. 17:311321.
77. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nature Med. 3:282286.
78. Platt, J. L. 1995. Hyperacute Xenograft Rejection. R.G. Landes, Austin, Tex.
79. Platt, J. L. 1998. New directions for organ transplantation. Nature 392(Suppl):1117.
80. Platt, J. L.,, R. J. Fischel,, A. J. Matas,, S. A. Reif,, R. M. Bolman,, and F. H. Bach. 1991. Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. Transplantation 52:214220.
81. Platt, J. L.,, T. W. LeBien,, and A. F. Michael. 1982. Interstitial mononuclear cell populations in renal graft rejection: identification by monoclonal antibodies in tissue sections. J. Exp. Med. 155:1730.
82. Platt, J. L.,, S. S. Lin,, and C. G. A. McGregor. 1998. Acute vascular rejection. Xenotransplantation 5:169175.
83. Platt, J. L.,, B. J. Lindman,, R. L. Geller,, H. J. Noreen,, J. L. Swanson,, A. P. Dalmasso,, and F. H. Bach. 1991. The role of natural antibodies in the activation of xenogenic endothelial cells. Transplantation 52:10371043.
84. Platt, J. L.,, and J. S. Logan,. 1997. The generation and use of transgenic animals for xenotransplantation, p. 455460. In L. M. Houdebine (ed.), Transgenic Animals: Generation and Use, 1st ed. Harwood Academic Publishers GmbH, Amsterdam, The Netherlands.
85. Platt, J. L.,, and J. S. Logan. 1996. Use of transgenic animals in xenotransplantation. Transplant. Rev. 10:6977.
86. Platt, J. L.,, G. M. Vercellotti,, A. P. Dalmasso,, A. J. Matas,, R. M. Bolman,, J. S. Najarian,, and F. H. Bach. 1990. Transplantation of discordant xenografts: a review of progress. Immunol. Today 11:450456.
87. Platt, J. L.,, G. M. Vercellotti,, B. J. Lindman,, T. R. OegemaJr.,, F. H. Bach,, and A. P. Dalmasso. 1990. Release of heparan sulfate from endothelial cells: implications for the pathogenesis of hyperacute rejection. J. Exp. Med. 171:13631368.
88. Powelson, J.,, A. B. Cosimi,, W. Austen,, M. BailenJr.,, R. Colvin,, P. Gianello,, T. Sablinski,, T. Lorf,, T. Kawai,, M. Tanaka,, and D. Sachs. 1994. Porcine-to-primate orthotopic liver transplantation. Transplant. Proc. 26:13531354.
89. Pruitt, S. K.,, A. D. Kirk,, R. R. Bollinger,, H. C. MarshJr.,, B. H. Collins,, J. L. Levin,, J. R. Mault,, J. S. Heinle,, S. Ibrahim,, A. R. Rudolph,, W. M. Baldwin III,, and F. Sanfilippo. 1994. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation 57:363370.
90. Reemtsma, K.,, B. H. McCracken,, J. U. Schlegel,, M. A. Pearl,, C. W. Pearce,, C. W. DeWitt,, P. E. Smith,, R. L. Hewitt,, R. L. Flinner,, and O. Creech. 1964. Renal heterotransplantation in man. Ann. Surg. 160:384410.
91. Rother, R. P.,, W. L. Fodor,, J. P. Springhorn,, C. W. Birks,, E. Setter,, M. S. Sandrin,, S. P. Squinto,, and S. A. Rollins. 1995. A novel mechanism of retrovirus inactivation in human serum mediated by anti-α-galactosyl natural antibody. J. Exp. Med. 182:13451355.
92. Saadi, S.,, N. S. Ihrcke,, and J. L. Platt,. 1996. Pathophysiology of xenograft rejection, p. 3145. In R. Lieberman, and R. Morris (ed.), Principles of Immunomodulatory Drug Development in Transplantation and Autoimmunity, 1st ed. Raven Press, New York, N.Y.
93. Saadi, S.,, and J. L. Platt,. 1998. Endothelial cell responses to complement activation, p. 335353. In J. E. Volanakis, and M. M. Frank (ed.), The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, N.Y.
94. Saadi, S.,, and J. L. Platt. 1995. Transient perturbation of endothelial integrity induced by antibodies and complement. J. Exp. Med. 181:2131.
95. Sablinski, T.,, D. Latinne,, P. Gianello,, M. Bailin,, K. Bergen,, R. B. Colvin,, A. Foley,, H. Hong,, T. Lorf,, S. Meehan,, R. Monroy,, J. A. Powelson,, M. Sykes,, M. Tanaka,, A. B. Cosimi,, and D. H. Sachs. 1995. Xenotransplantation of pig kidneys to nonhuman primates: I. development of the model. Xenotransplantation 2:264270.
96. Sachs, D. H.,, and T. Sablinski. 1995. Tolerance across discordant xenogeneic barriers. Xenotransplantation 2:234239.
97. Sandrin, M. S.,, W. L. Fodor,, E. Mouhtouris,, N. Osman,, S. Cohney,, S. A. Rollins,, E. R. Guilmette,, E. Setter,, S. P. Squinto,, and I. McKenzie. 1995. Enzymatic remodelling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nat. Med. 1:12611267.
98. Sandrin, M. S.,, H. A. Vaughan,, P. L. Dabkowski,, and I. F. C. McKenzie. 1993. Anti-pig IgM antibodies in human serum react predominantly with Gala(l ,3)Gal epitopes. Proc. Nat. Acad. Sci. USA 90:1139111395.
99. Schmoeckel, M.,, F. N. K. Bhatti,, A. Zaidi,, E. Cozzi,, P. D. Waterworth,, M. J. Tolan,, M. Goddard,, R. G. Warner,, G. A. Langford,, J. J. Dunning,, J. Wallwork,, and D. J. G. White. 1998. Orthotopic heart transplantation in a transgenic pig-to-primate model. Transplantation 65:15701577.
100. Selvan, R. S.,, H. B. Kapadia,, and J. L. Platt. 1998. Complement-induced expression of chemokine genes in endothelium: regulation by IL-1-dependent and -independent mechanisms. J. Immunol. 161:43884395.
101. Sharma, A.,, J. F. Okabe,, P. Birch,, J. L. Platt,, and J. S. Logan. 1996. Reduction in the level of Gal (α?1,3) Gal in transgenic mice and pigs by the expression of an a( 1,2) fucosyltransferase. Proc. Nat. Acad. Sci. USA 93:71907195.
102. Starzl, T. E.,, A. J. Demetris,, N. Murase,, S. Ildstad,, C. Ricordi,, and M. Trucco. 1992. Cell migration, chimerism, and graft acceptance. Lancet 339:15791582.
103. Starzl, T. E.,, J. Fung,, A. Tzakis,, S. Todo,, A. J. Demetris,, I. R. Marino,, H. Doyle,, A. Zeevi,, V. Warty,, M. Michaels,, S. Kusne,, W. A. Rudert,, and M. Trucco. 1993. Baboon-to-human liver transplantation. Lancet 341:6571.
104. Starzl, T. E.,, T. L. Marchioro,, G. N. Peters,, C. H. Kirkpatrick,, W. E. C. Wilson,, K. A. Porter,, D. Rifkind,, D. A. Ogden,, C. R. Hitchcock,, and W. R. Waddell. 1964. Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation 2:752776.
105. Takahashi, T.,, S. Saadi,, and J. Platt. 1997. Recent advances in the immunology of xenotransplantation. Immunol. Res. 16:273297.
106. Ullman, E. 1914. Tissue and organ transplantation. Ann. Surg. 60:195219.
107. Yamada, K.,, D. H. Sachs,, and H. DerSimonian. 1995. Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition. J. Immunol. 155:52495256.
108. Yang, Y.-G.,, E. deGoma,, H. Ohdan,, J. L. Bracy,, Y. Xu,, J. Iacomini,, A. D. Thall,, and M. Sykes. 1998. Tolerization of anti-Galα1-3Gal natural antibody-forming B cells by induction of mixed chimerism. J. Exp. Med. 187:13351342.
109. Ye, Y.,, F. A. Neethling,, M. Niekrasz,, E. Koren,, S. V. Richards,, M. Martin,, S. Kosanke,, R. Oriol,, and D. K. C. Cooper. 1994. Evidence that intravenously administered α-galactosyl carbohydrates reduce baboon serum cytotoxicity to pig kidney cells (PK15) and transplanted pig hearts. Transplantation 58:330337.
110. Zaidi, A.,, P. Friend,, M. Schmoeckel,, F. N. K. Bhatti,, M. Tolan,, P. Waterworth,, E. Cozzi,, G. Chavez,, J. J. Dunning,, J. Wallwork,, and D. J. G. White. 1997. Hyperacute rejection is not consistent after pig to primate renal xenotransplantation (abstract). Presented at the 4th International Congress for Xenotransplantation, Nantes, France.
111. Zaidi, A.,, M. Schmoeckel,, F. Bhatti,, P. Waterworth,, M. Tolan,, E. Cozzi,, G. Chavez,, G. Langford,, S. Thiru,, J. Wallwork,, D. White,, and P. Friend. 1998. Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors. Transplantation 65:15841590.
112. Zehr, K. J.,, A. Herskowitz,, P. C. Lee,, P. Kumar,, A. M. Gillinov,, and W. A. Baumgartner. 1994. Neutrophil adhesion and complement inhibition prolongs survival of cardiac xenografts in discordant species. Transplantation 57:900906.
113. Zhao, Y.,, K. Swenson,, J. J. Sergio,, J. S. Arn,, D. H. Sachs,, and M. Sykes. 1996. Skin graft tolerance across a discordant xenogeneic barrier. Nature Med. 2:12111216.


Generic image for table
Table 1

Xenograft classification

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1
Generic image for table
Table 2

Activation of complement via the alternative pathway on xenogeneic cells

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1
Generic image for table
Table 3

Factors implicated in the initiation of acute vascular rejection

Citation: Platt J. 2001. A Primer on Xenotransplantation, p 3-28. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch1

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error