DOI QR코드

DOI QR Code

Porcine Xenotransplantation to Primates

  • Min, T.S. ;
  • Han, H.J. ;
  • Park, S.H.
  • Received : 2010.08.20
  • Accepted : 2010.09.29
  • Published : 2010.11.01

Abstract

Xenotransplantation is a hot topic currently, since the demand for diverse organs is increasing in patients. Among many species, pigs are suitable animals for xenotranplantation as they share many anatomical and physiological characteristics with humans. This review article provides an overview of porcine xenotransplantation and the rejection of pig xenotransplants in primates, and use of genetically modified and cloned pigs in xenotransplantation. It also highlights major target organs in porcine xenotransplantation and virus infection in xenotransplantation.

Keywords

Xenotransplantation;Pig;Rejection;Virus Infection

References

  1. Bauer, A., J. Postrach, M. Thormann, S. Blanck, C. Faber, B.Wintersperger, S. Michel, J. M. Abicht, F. Christ, C. Schmitz,M. Schmoeckel, B. Reichart and P. Brenner. 2010. First experience with heterotopic thoracic pig-to-baboon cardiac xenotransplantation. Xenotransplantation 17:243-249. https://doi.org/10.1111/j.1399-3089.2010.00587.x
  2. Brunetti, D., I. Lagutina, S. Colleoni, R. Duchi, F. Calabrese, M.Seveso, E. Cozzi, G. Lazzari, F. Lucchini and C. Galli. 2008.Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts. Cloning Stem Cells 10:409-419. https://doi.org/10.1089/clo.2008.0036
  3. Buhler, L., M. Basker, I. P. Alwayn, C. Goepfert, H. Kitamura, T.Kawai, S. Gojo, T. Kozlowski, E. L. Ierino, M. Awwad, D. H.Sachs, R. Sackstein, S. C. Robson and D. K. Cooper. 2000. Coagulation and thrombotic disorders associated with pig organ and hematopoietic cell transplantation in nonhuman primates. Transplantation 70:1323-1331. https://doi.org/10.1097/00007890-200011150-00010
  4. 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 63:149-155. https://doi.org/10.1097/00007890-199701150-00027
  5. Cabot, R. A., B. Kuhholzer, A. W. Chan, L. Lai, K. W. Park, K. Y.Chong, G. Schatten, C. N. Murphy, L. R. Abeydeera, B. N.Day and R. S. Prather. 2001. Transgenic pigs produced using in vitro matured oocytes infected with a retroviral vector. Anim. Biotechnol. 12:205-214. https://doi.org/10.1081/ABIO-100108347
  6. Cardona, K., G. S. Korbutt, Z. Milas, J. Lyon, J. Cano, W. Jiang, H.Bello-Laborn, B. Hacquoil, E. Strobert, S. Gangappa, C. J.Weber, T. C. Pearson, R. V. Rajotte and C. P. Larsen. 2006. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat. Med. 12:304-306. https://doi.org/10.1038/nm1375
  7. Chen, G., H. Qian, T. Starzl, H. Sun, B. Garcia, X. Wang, Y. Wise,Y. Liu, Y. Xiang, L. Copeman, W. Liu, A. Jevnikar, W. Wall, D.K. Cooper, N. Murase, Y. Dai, W. Wang, Y. Xiong, D. J. Whiteand R. Zhong. 2005. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat. Med. 11:1295-1298. https://doi.org/10.1038/nm1330
  8. Chen, G., H. Sun, H. Yang, D. Kubelik, B. Garcia, Y. Luo, Y.Xiang, A. Qian, L. Copeman, W. Liu, C. J. Cardella, W. Wang,Y. Xiong, W. Wall, D. J. White and R. Zhong. 2006. The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy. Transplantation 81:273-283. https://doi.org/10.1097/01.tp.0000188138.53502.de
  9. Cooper, D. K. and A. Casu. 2009. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 4: Pre-clinical efficacy and complication data required to justify a clinical trial. Xenotransplantation 16:229-238. https://doi.org/10.1111/j.1399-3089.2009.00543.x
  10. Cooper, D. K. and J. J. Teuteberg. 2010. Pig heart xenotransplantation as a bridge to allotransplantation. J. Heart Lung Transplant. 29:838-840. https://doi.org/10.1016/j.healun.2010.03.017
  11. Cooper, D. K., A. Keogh, J. Brink, P. A. Corris, W. Klepetko, R. N.Pierson, M. Schmoeckel, R. Shirakura and L. WarnerStevenson L. 2000. Report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation: the present status of xenotransplantation and its potential role in the treatment of end-stage cardiac and pulmonary diseases. J. Heart Lung Transplant. 19:1125-1165. https://doi.org/10.1016/S1053-2498(00)00224-2
  12. Cooper, D. K., B. Gollackner and D. H. Sachs. 2002. Will the pig solve the transplantation backlog? Annu. Rev. Med. 53:133. https://doi.org/10.1146/annurev.med.53.082901.103900
  13. Cooper, D. K., E. Koren and R. Oriol. 1993. Genetically engineered pigs. Lancet 342: 682-683. https://doi.org/10.1016/0140-6736(93)91791-J
  14. Cozzi, E., A. W. Tucker, G. A. Langford, G. Pino-Chavez, L.Wright, M. J. O'Connell, V. J. Young, R. Lancaster, M.McLaughlin, K. Hunt, M. C. Bordin and D. J. White. 1997. Characterization of pigs transgenic for human decayaccelerating factor. Transplantation 64:1383-1392. https://doi.org/10.1097/00007890-199711270-00002
  15. d'Apice, A. J. and P. J. Cowan. 2009. Xenotransplantation: the next generation of engineered animals. Transpl Immunol. 21:111-115. https://doi.org/10.1016/j.trim.2008.10.003
  16. Denner, J., H. J. Schuurman and C. Patience. 2009. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-chapter 5: Strategies to prevent transmission of porcine endogenous retroviruses. Xenotransplantation 16:239-248. https://doi.org/10.1111/j.1399-3089.2009.00544.x
  17. Diamond, L. E., C. M. Quinn, M. J. Martin, J. Lawson, J. L. Plattand J. S. Logan. 2001. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation 71:132-142. https://doi.org/10.1097/00007890-200101150-00021
  18. Dieckhoff, B., A. Karlas, A. Hofmann, W. A. Kues, B. Petersen, A.Pfeifer, H. Niemann, R. Kurth and J. Denner. 2007. Inhibition of porcine endogenous retroviruses (PERVs) in primary porcine cells by RNA interference using lentiviral vectors. Arch. Virol. 152:629-634. https://doi.org/10.1007/s00705-006-0868-y
  19. Diswall, M., J. Angström, H. Karlsson, C. J. Phelps, D. Ayares, S.Teneberg and M. E. Breimer. 2010. Structural characterization of alpha1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies. Xenotransplantation 17:48-60. https://doi.org/10.1111/j.1399-3089.2009.00564.x
  20. Ekser, B., B. Gridelli, A. J. Tector and D. K. Cooper. 2009. Pig liver xenotransplantation as a bridge to allotransplantation: which patients might benefit? Transplantation 88:1041-1049. https://doi.org/10.1097/TP.0b013e3181ba0555
  21. Ekser, B., G. J. Echeverri, A. C. Hassett, M. H. Yazer, C. Long, M.Meyer, M. Ezzelarab, C. C. Lin, H. Hara, D. J. van der Windt,E. M. Dons, C. Phelps, D. Ayares, D. K. Cooper and B. Gridelli. 2010. Hepatic function after genetically engineered pig liver transplantation in baboons. Transplantation (in press)
  22. Ekser, B., P. Rigotti, B. Gridelli and D. K. Cooper. 2009. Xenotransplantation of solid organs in the pig-to-primate model. Transpl. Immunol. 21:87-92. https://doi.org/10.1016/j.trim.2008.10.005
  23. Gewartowska, M. and W. L. Olszewski. 2007. Hepatocyte transplantation-biology and application. Ann. Transplant. 12:27-36.
  24. Ezzelarab, M., B. Garcia, A. Azimzadeh, H. Sun, C. C. Lin, H.Hara, S. Kelishadi, T. Zhang, Y. J. Lin, H. C. Tai, R. Wagner, J.Thacker, N. Murase, K. McCurry, R. N. Barth, D. Ayares, R. N.Pierson 3rd and D. K. Cooper. 2009. The innate immune response and activation of coagulation in alpha1,3-galactosyltransferase gene-knockout xenograft recipients. Transplantation 87:805-812. https://doi.org/10.1097/TP.0b013e318199c34f
  25. Good, A. H., D. K. 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. 24:559-562.
  26. Hara, H., B. Gridelli, Y. J. Lin, A. Marcos and D. K. Cooper. 2008.Liver xenografts for the treatment of acute liver failure: clinical and experimental experience and remaining immunologic barriers. Liver Transpl. 14:425-434. https://doi.org/10.1002/lt.21476
  27. Hering, B. J., M. Wijkstrom, M. L. Graham, M. Hårdstedt, T. C.Aasheim, T. Jie, J. D. Ansite, M. Nakano, J. Cheng, W. Li, K.Moran, U. Christians, C. Finnegan, N. Kirchhof and H. J.Schuurman. 2006. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat. Med. 12:301-303. https://doi.org/10.1038/nm1369
  28. Hisashi, Y., K. Yamada, K. Kuwaki, Y. L. Tseng, F. J. Dor, S. L.Houser, S. C. Robson, H. J. Schuurman, D. K. Cooper, D. H.Sachs, R. B. Colvin and A. Shimizu. 2008. Rejection of cardiac xenografts transplanted from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons. Am. J. Transplant. 8:2516-2526. https://doi.org/10.1111/j.1600-6143.2008.02444.x
  29. Hofmann, A., B. Kessler, S. Ewerling, M. Weppert, B. Vogg, H.Ludwig, M. Stojkovic, M. Boelhauve, G. Brem, E. Wolf and A.Pfeifer. 2003. Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep. 4:1054-1060. https://doi.org/10.1038/sj.embor.7400007
  30. Horvath, K. A., P. C. Corcoran, A. K. Singh, R. F. Hoyt, C. Carrier,M. L. 3rd Thomas and M. M. Mohiuddin. 2010. Left ventricular pressure measurement by telemetry is an effective means to evaluate transplanted heart function in experimental heterotopic cardiac xenotransplantation. Transplant. Proc. 42:2152-2155. https://doi.org/10.1016/j.transproceed.2010.05.117
  31. Hughes, H. C. 1986. Swine in cardiovascular research. Lab. Anim. Sci. 36:348-350.
  32. Inverardi, L. and R. Pardi. 1994. Early events in cell-mediated recognition of vascularized xenografts: cooperative interactions between selected lymphocyte subsets and natural antibodies. Immunol. Rev. 141:71-93. https://doi.org/10.1111/j.1600-065X.1994.tb00873.x
  33. Issa, N. C., R. A. Wilkinson, A. Griesemer, D. K. Cooper, K.Yamada, D. H. Sachs and J. A. Fishman. 2008. Absence of replication of porcine endogenous retrovirus and porcine lymphotropic herpesvirus type 1 with prolonged pig cell microchimerism after pig-to-baboon xenotransplantation. J. Virol. 82:12441-12448. https://doi.org/10.1128/JVI.01278-08
  34. Kamar, N., J. Selves, J. M. Mansuy, L. Ouezzani, J. M. Péron, J.Guitard, O. Cointault, L. Esposito, F. Abravanel, M. Danjoux,D. Durand, J. P. Vinel, J. Izopet and L. Rostaing. 2008. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358:811-817. https://doi.org/10.1056/NEJMoa0706992
  35. Kawai, T., D. Andrews, R. B. Colvin, D. H. Sachs and A. B.Cosimi. 2000. Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat. Med. 6:114.
  36. Kirk, A. D. and D. M. Harlan. 2001. Reply: Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat. Med. 6:114.
  37. Khalfoun, B., D. Barrat, H. Watier, M. C. Machet, B. Arbeille-Brassart, J. G. Riess, H. Salmon, Y. Gruel, P. Bardos and Y.Lebranchu. 2000. Development of an ex vivo model of pig kidney perfused with human lymphocytes. Analysis of xenogeneic cellular reactions. Surgery 128:447-457
  38. Kirkeby, S. and H. B. Mikkelsen. 2008. Distribution of the alphaGal- and the non-alphaGal T-antigens in the pig kidney: potential targets for rejection in pig-to-man xenotransplantation. Immunol Cell Biol. 86:363-371. https://doi.org/10.1038/icb.2008.1
  39. Klymiuk, N., B. Aigner, G. Brem and E. Wolf. 2010. Genetic modification of pigs as organ donors for xenotransplantation. Mol. Reprod. Dev. 77:209-221.
  40. Knosalla, C., K. Yazawa, A. Behdad, N. Bodyak, H. Shang, L.Bühler, S. Houser, B. Gollackner, A. Griesemer, I. Schmitt-Knosalla, H. J. Schuurman, M. Awwad, D. H. Sachs, D. K.Cooper, K. Yamada, A. Usheva and S. C. Robson. 2009. Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation. Am. J. Transplant. 9:1006-1016. https://doi.org/10.1111/j.1600-6143.2009.02602.x
  41. Komoda, H., S. Miyagawa, T. Omori, Y. Takahagi, H. Murakami,T. Shigehisa, T. Ito, H. Matsuda and R. Shirakura. 2005.Survival of adult islet grafts from transgenic pigs with Nacetylglucosaminyltransferase-III (GnT-III) in cynomolgus monkeys. Xenotransplantation 12:209-216. https://doi.org/10.1111/j.1399-3089.2005.00206.x
  42. Lavitrano, M., M. Busnelli, M. G. Cerrito, R. Giovannoni, S. Manzini and A. Vargiolu. 2006. Sperm-mediated gene transfer. Reprod. Fertil. Dev. 18:19-23. https://doi.org/10.1071/RD05124
  43. Lee, H., B. Lee, Y. Kim, N. Paik and H. Rho. 2010.Characterization of transgenic pigs that express human decay accelerating factor and cell membrane-tethered human tissue factor pathway inhibitor. Reprod. Domest. Anim. (in press)
  44. Li, L., D. Pang, T. Wang, Z. Li, L. Chen, M. Zhang, N. Song, D.Nie, Z. Chen, L. Lai and H. Ouyang. 2009. Production of a reporter transgenic pig for monitoring Cre recombinase activity. Biochem. Biophys. Res. Commun. 382:232-235. https://doi.org/10.1016/j.bbrc.2009.02.146
  45. Lila, N., C. G. McGregor, S. Carpentier, J. Rancic, G. W. Byrne and A. Carpentier. 2010. Gal knockout pig pericardium: new source of material for heart valve bioprostheses. J. Heart Lung Transplant. 29:538-543. https://doi.org/10.1016/j.healun.2009.10.007
  46. Lin, C. C., D. K. Cooper and A. Dorling. 2009. Coagulation dysregulation as a barrier to xenotransplantation in the primate. Transpl. Immunol. 21:75-80. https://doi.org/10.1016/j.trim.2008.10.008
  47. Lin, C. C., M. Ezzelarab, R. Shapiro, B. Ekser, C. Long, H. Hara,G. Echeverri, C. Torres, H. Watanabe, D. Ayares, A. Dorling and D. K. Cooper. 2010. Recipient tissue factor expression is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation. Am. J. Transplant. 10:1556-1568. https://doi.org/10.1111/j.1600-6143.2010.03147.x
  48. Lunney, J. K. 2007. Advances in swine biomedical model genomics. Int. J. Biol. Sci. 3:179-184. https://doi.org/10.3923/ijb.2007.179.187
  49. Makowa, L., D. V. Cramer, A. Hoffman, M. Breda, L. Sher, G.Eiras-Hreha, P. J. Tuso, C. Yasunaga, C. A. Cosenza and G. D.Wu. 1995. The use of pig liver xenograft for temporary support of a patient with fulminant hepatic failure. Transplantation 59:1654-1659. https://doi.org/10.1097/00007890-199506270-00002
  50. Manzini, S., A. Vargiolu, I. M. Stehle, M. L. Bacci, M. G. Cerrito,R. Giovannoni, A. Zannoni, M. R. Bianco, M. Forni, P. Donini,M. Papa, H. J. Lipps and M. Lavitrano. 2006. Genetically modified pigs produced with a nonviral episomal vector. Proc. Natl. Acad. Sci. USA. 103:17672-17677. https://doi.org/10.1073/pnas.0604938103
  51. Meije, Y., R. R. Tonjes and J. A. Fishman. 2010. Retroviral restriction factors and infectious risk in xenotransplantation. Am. J. Transplant. 10:1511-1516. https://doi.org/10.1111/j.1600-6143.2010.03146.x
  52. Mueller, N. J., C. Livingston, C. Knosalla, R. N. Barth, S.Yamamoto, B. Gollackner, F. J. Dor, L. Buhler, D. H. Sachs, K.Yamada, D. K. Cooper and J. A. Fishman. 2004. Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation. J. Infect. Dis. 189:1628-1633. https://doi.org/10.1086/383351
  53. Pereira-Sampaio, M. A., L. A. Favorito and F. J. Sampaio. 2004.Pig kidney: anatomical relationships between the intrarenal arteries and the kidney collecting system. Applied study for urological research and surgical training. J. Urol. 172:2077- 2081. https://doi.org/10.1097/01.ju.0000138085.19352.b5
  54. Petersen, B., W. Ramackers, A. Tiede, A. Lucas-Hahn, D.Herrmann, B. Barg-Kues, W. Chuettler, L. Friedrich, R.Schwinzer, M. Winkler and H. Niemann. 2009. Pigs transgenic for human thrombomodulin have elevated production of activated protein C. Xenotransplantation 16:486-495. https://doi.org/10.1111/j.1399-3089.2009.00537.x
  55. Pierson, R. N. 3rd., A. Dorling, D. Ayares, M. A. Rees, J. D.Seebach, J. A. Fishman, B. J. Hering and D. K. Cooper. 2009. Current status of xenotransplantation and prospects for clinical application. Xenotransplantation 16:263-280. https://doi.org/10.1111/j.1399-3089.2009.00534.x
  56. Pierson, R. N. III. 2009. Antibody-mediated xenograft injury: mechanisms and protective strategies. Transpl. Immunol. 21: 65-69. https://doi.org/10.1016/j.trim.2009.03.008
  57. Platt, J. L. 1998. New directions for organ transplantation. Nature 392:11-17. https://doi.org/10.1038/32023
  58. Prather, R. S., R. J. Hawley, D. B. Carter, L. Lai and J. L. Greenstein. 2003. Transgenic swine for biomedicine and agriculture. Theriogenology 59:115-123. https://doi.org/10.1016/S0093-691X(02)01263-3
  59. Puga Yung, G., M. K. Schneider and J. D. Seebach. 2009. Immune responses to alpha1,3 galactosyltransferase knockout pigs. Curr. Opin. Organ Transplant. 14:154-160. https://doi.org/10.1097/MOT.0b013e328329250d
  60. Qv, J., G. Chen, Z. Shen, G. Jiang, J. Ding, W. Gao, and C. Chen.2009. Activation of complement in the discordant heart xenotransplantation of pig-to-monkey model and the impact of intrathymic inoculation of xenogeneic antigen combined with whole-body gamma-radiation. Transplant. Proc. 41:3905-3908. https://doi.org/10.1016/j.transproceed.2009.05.038
  61. Ramirez, P., J. Yelamos, P. Parrilla and R. Chavez. 2001. Hepatic xenotransplantation will benefit from strategies aimed to reduce complement activation. Liver Transpl. 7:562-563. https://doi.org/10.1053/jlts.2001.0070562
  62. Ramirez, P., R. Chavez, M. Majado, V. Munitiz, A. Muñoz, Q.Hernandez, C. G. Palenciano, G. Pino-Chavez, M. Loba, A.Minguela, J. Yelamos, M. R. Gago, A. S. Vizcaino, H. Asensi,M. G. Cayuela, B. Segura, F. Marin, A. Rubio, T. Fuente, R.Robles, F. S. Bueno, T. Sansano, F. Acosta, J. M. Rodriguez, F.Navarro, J. Cabezuelo, E. Cozzi, D. J. White, R. Y. Calne and P.Parrilla. 2000. Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days. Transplantation 70:989-998. https://doi.org/10.1097/00007890-200010150-00001
  63. Ravelingien, A., F. Mortier, E. Mortier, I. Kerremans and J. Braeckman. 2004. Proceeding with clinical trials of animal to human organ transplantation: a way out of the dilemma. J. Med. Ethics. 30:92-98. https://doi.org/10.1136/jme.2003.004325
  64. Rogers, S. A., F. Chen, M. Talcott, H. Liapis and M. R.Hammerman. 2006. Glucose tolerance normalization following transplantation of pig pancreatic primordia into nonimmunosuppressed diabetic ZDF rats. Transpl. Immunol. 16:176-184. https://doi.org/10.1016/j.trim.2006.08.007
  65. Rogers, S. A., F. Chen, M. R. Talcott, C. Faulkner, J. M. Thomas,M. Thevis and M. R. 2007. Hammerman. Long-term engraftment following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic rhesus macaques. Xenotransplantation 14:591-602. https://doi.org/10.1111/j.1399-3089.2007.00429.x
  66. Sachs, D. H. and C. Galli. 2009. Genetic manipulation in pigs. Curr. Opin. Organ Transplant. 14:148-153. https://doi.org/10.1097/MOT.0b013e3283292549
  67. Shimizu, A. and K. Yamada. 2006. Pathology of renal xenograft rejection in pig to non-human primate transplantation. Clin. Transplant. 20:46-52. https://doi.org/10.1111/j.1399-0012.2006.00550.x
  68. Shimizu, A., Y. Hisashi, K. Kuwaki, Y. L. Tseng, F. J. Dor, S. L.Houser, S. C. Robson, H. J. Schuurman, D. K. Cooper, D. H.Sachs, K. Yamada and R. B. Colvin. 2008. Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons. Am. J. Pathol. 172:1471-1481. https://doi.org/10.2353/ajpath.2008.070672
  69. Smolenski, R. T., M. Forni, M. Maccherini, M. L. Bacci, E. M.Slominska, H. Wang, P. Fornasari, R. Giovannoni, F. Simeone,A. Zannoni, G. Frati, K. Suzuki, M. H. Yacoub and M.Lavitrano. 2007. Reduction of hyperacute rejection and protection of metabolism and function in hearts of human decay accelerating factor (hDAF)-expressing pigs. Cardiovasc. Res. 73:143-152. https://doi.org/10.1016/j.cardiores.2006.10.027
  70. Stiegler, P., V. Stadlbauer, F. Hackl, S. Schaffellner, F. Iberer, J.Greilberger, D. Strunk, S. Zelzer, C. Lackner and K. Tscheliessnigg. 2010. Prevention of oxidative stress in porcine islet isolation. J. Artif. Organs 13:38-47. https://doi.org/10.1007/s10047-010-0488-x
  71. Tector, A. J., M. Berho, J. A. Fridell, A. DiCarlo, S. Liu, C.Soderland, J. S. Barkun, P. Metrakos and J. I. Tchervenkov. 2001. Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation. Liver Transpl. 7:82-89. https://doi.org/10.1053/jlts.2001.21281
  72. Teotia, S. S., R. C. Walker, J. M. Schirmer, H. D. Tazelaar, M. G.Michaels, J. M. Risdahl, G. W. Byrne, J. S. Logan and C. G.McGregor. 2005. Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival. Xenotransplantation 12:127-133. https://doi.org/10.1111/j.1399-3089.2005.00205.x
  73. Thomas, F. T., T. Ljung, J. Henretta, K. Pittman and J. Thomas.1995. Reversal of type II (NIDDM) diabetes by pancreas islet transplantation: an emerging new concept in pathophysiology of an enigmatic disease. Transplant. Proc. 27:3167-3169.
  74. Tuso, P. J., D. V. Cramer, C. Yasunaga, C. A. Cosenza, G. D. Wuand L. Makowka. 1993. Removal of natural human xenoantibodies to pig vascular endothelium by perfusion of blood through pig kidneys and livers. Transplantation 55:1375-1378. https://doi.org/10.1097/00007890-199306000-00031
  75. van der Windt, D. J., G. J. Echeverri, J. N. Ijzermans and D. K.Cooper. 2008. The choice of anatomical site for islet transplantation. Cell Transplant. 17:1005-1014. https://doi.org/10.3727/096368908786991515
  76. van der Windt, D. J., R. Bottino, A. Casu, N. Campanile, C.Smetanka, J. He, H. Murase, H. Hara, S. Ball, B. E. Loveland,D. Ayares, F. G. Lakkis, D. K. Cooper and M. Trucco. 2009.Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am. J. Transplant. 9:2716-2726. https://doi.org/10.1111/j.1600-6143.2009.02850.x
  77. Vodicka, P., K. Jr. Smetana, B. Dvorankova, T. Emerick, Y. Z. Xu,J. Ourednik, V. Ourednik and J. Motlik. 2005. The miniature pig as an animal model in biomedical research. Ann. NY Acad. Sci. 1049:161-171. https://doi.org/10.1196/annals.1334.015
  78. Weiss, E. H., B. G. Lilienfeld, S. Müller, E. Müller, N. Herbach, B.Kessler, R. Wanke, R. Schwinzer, J. D. Seebach, E. Wolf and G.Brem. 2009. HLA-E/human beta2-microglobulin transgenic pigs: protection against xenogeneic human anti-pig natural killer cell cytotoxicity. Transplantation 87:35-43. https://doi.org/10.1097/TP.0b013e318191c784
  79. Whitelaw, C. B., P. A. Radcliffe, W. A. Ritchie, A. Carlisle, F. M.Ellard, R. N. Pena, J. Rowe, A. J. Clark, T. J. King and K. A.Mitrophanous. 2004. Efficient generation of transgenic pigs using equine infectious anaemia virus (EIAV) derived vector. FEBS Lett. 571:233-236. https://doi.org/10.1016/j.febslet.2004.06.076
  80. Yu, P., P. Zhang, L. Zhang, S. F. Li, J. Q. Cheng, Y. R. Lu, Y. P. Li and H. Bu. 2009. Studies on long-term infection of human cells with porcine endogenous retrovirus. Acta Virol. 53:169-174. https://doi.org/10.4149/av_2009_03_169