Abstract
Human allotransplantation has been very successful over the past six decades. Heart and kidney transplantations remain the therapy of choice for end-stage organ failure. Although surgical competence is available in many medical centres around the world, the demand for organs far exceeds the supply from human donors. The consequences for patients waiting for transplants are severe, as can be seen by the following two examples. In Germany, the annual mortality for waiting heart transplant candidates is 18 %. The average waiting time for a cadaveric kidney is five years, which significantly reduces the prospects for patients eventually receiving a donated kidney, because graft survival drops substantially after extended dialysis .
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Notes
- 1.
Rahmel (2013).
- 2.
Meier-Kriesche and Kaplan (2002).
- 3.
Reichenspurner et al. (1989).
- 4.
Cozzi et al. (2009).
- 5.
Nagata et al. (2007).
- 6.
Leveque et al. (2011).
- 7.
Hara and Cooper (2011).
- 8.
Hossain et al. (2007).
- 9.
Collaborative Islet Transplant Registry (2013).
- 10.
- 11.
- 12.
van der Windt et al. (2009).
- 13.
Kouchoukos et al. (2012).
- 14.
Kasimir et al. (2006).
- 15.
- 16.
Le Tissier et al. (1997).
- 17.
- 18.
Bartosch et al. (2004).
- 19.
- 20.
- 21.
Galili (2013).
- 22.
Phelps et al. (2003).
- 23.
Ekser et al. (2011).
- 24.
Yamada et al. (2005).
- 25.
- 26.
- 27.
- 28.
- 29.
Petersen et al. (2011).
- 30.
- 31.
Roussel et al. (2008).
- 32.
Peterson et al. (2009); Wünsch et al. (2014).
- 33.
Palumbo and Anderson (2011).
- 34.
Heinzelmann et al. (2008).
- 35.
- 36.
Klymiuk et al. (2012).
- 37.
Ekser et al. (2012).
- 38.
Dufrane et al. (2010).
- 39.
Van der Windt et al. (2009).
- 40.
Mohiuddin et al. (2012, 2014, and personal communication)
- 41.
- 42.
- 43.
Baldan et al. (2004).
- 44.
- 45.
Calafiore et al. (2004).
- 46.
Elliot et al. (2011, and personal communication).
- 47.
Wynyard et al. (2014).
- 48.
References
Badin, R.A., A. Padoan, and M. Vadori, et al. 2010. Long-term clinical recovery in parkinsonian monkey recipients of CTLA4-Ig transgenic porcine neural precursors. Transplantation 90 (Suppl 2): 47.
Baldan, N., P. Rigotti, and F. Calabrese, et al. 2004. Ureteral stenosis in hDAF pig-to-primate renal xenotransplantation: A phenomenon related to immunological events? American Journal of Transplantation 4 (4): 475–481.
Bartosch, B., D. Stefanidis, and R. Myers, et al. 2004. Evidence and consequence of porcine endogenous retrovirus recombination. Journal of Virology 78 (24): 13880–13890.
Bauer, A., J. Postrach, and M. Thormann, et al. 2010. First experience with heterotopic thoracic pig-to-baboon cardiac xenotransplantation. Xenotransplantation 17 (3): 243–249.
Byrne, G. W., P. G. Stalboerger, and Z. Du, et al. 2011. Identification of new carbohydrate and membrane protein antigens in cardiac xenotransplantation. Transplantation 91 (3): 287–292.
Calafiore, R., G. Basta, and G. Luca, et al. 2004. Grafts of microencapsulated pancreatic islet cells for the therapy of diabetes mellitus in non-immunosuppressed animals. Biotechnology and Applied Biochemistry 39(Pt 2): 159–164.
Cantu, E., K. R. Balsara, and B. Li, et al. 2007. Prolonged function of macrophage, von Willibrand factor-deficient porcine pulmonary xenografts. American Journal of Transplantation 7 (1): 66–75.
Cardona, K., G. S. Korbutt, and Z. Milas, et al. 2006. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nature Medicine 12 (3): 304–306.
Choi, H. J., M. K. Kim, and H. J. Lee, et al. 2011. Efficacy of pig-to-rhesus lamellar corneal xenotransplantation. Investigative Ophthalmology and Visual Science 52 (9): 6643–6650.
Collaborative Islet Transplant Registry. 2013. www.citeregistry.org. Accessed 6 June 2015.
Corcoran, P. C., K. A. Horvath, and A. K. Singh, et al. 2010. Surgical and nonsurgical complications of a pig to baboon heterotopic heart transplantation model. Transplantation Proceedings 42 (6): 2149–2151.
Cowan, P. J., J. C. Roussel, and A. J. d’Apice. 2009. The vascular and coagulation issues in xenotransplantation. Current Opinion Organ Transplantation 14 (2): 161–167.
Cozzi, E., M. Tallacchini, and E. B. Flanagan, et al. 2009. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes. Chapter 1: Key ethical requirements and progress toward the definition of an international regulatory framework. Xenotransplantation 16 (4): 203–214.
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 (4): 239–248.
Diswall, M., J. Angstrom, and H. Karlsson, et al. 2010. Structural characterization of alpha1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies. Xenotransplantation 17 (1): 48–60.
Dufrane, D., R. M. Goebbels, P. Gianello. 2010. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation 90 (10): 1054–1062.
Ekser, B., G. Kumar, M. Veroux, and D. K. Cooper. 2011. Therapeutic issues in the treatment of vascularized xenotransplants using gal-knockout donors in nonhuman primates. Current Opinion Organ Transplantation 16 (2): 222–230.
Ekser, B., M. Ezzelarab, and H. Hara, et al. 2012. Clinical xenotransplantation: The next medical revolution? Lancet 379 (9816): 672–83.
Elliott, R. B. 2011. Living cell technologies. Towards xenotransplantation of pig islets in the clinic. Current Opinion Organ Transplantation 16 (2): 195–200.
Ezzelarab, M., B. Garcia, and A. Azimzadeh, et al. 2009. The innate immune response and activation of coagulation in alpha1,3-galactosyltransferase gene-knockout xenograft recipients. Transplantation 87 (6): 805–812.
Fishmann, J. A., S. Scobie, and Y. Takeuchi. 2011. Annex 4. Xenotransplantation-associated infectious risk: A background paper for the second WHO global consultation on regulatory requirements for Xenotransplantation clinical trials. Geneva, Switzerland, 17–19 October 2011. http://www.who.int/transplantation/xeno/en/. Accessed 20 April 2015.
Galili, U. 2013. Discovery of the natural anti-Gal antibody and its past and future relevance to medicine. Xenotransplantation 20 (3): 138–147.
Garkavenko, O., B. Dieckhoff, and S. Wynyard, et al. 2008a. Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study. Journal of Medical Virology 80 (11): 2046–2052.
Garkavenko, O., S. Wynyard, and D. Nathu, et al. 2008b. Porcine endogenous retrovirus (PERV) and its transmission characteristics: A study of the New Zealand designated pathogen-free herd. Cell Transplantation 17 (12): 1381–1388.
Hara H, and Cooper, D. K. 2011. Xenotransplantation—The future of corneal transplantation? Cornea 30 (4): 371–378.
Heinzelmann, F., P. J. Lang, and H. Ottinger, et al. 2008. Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation. International Journal of Radiation Oncology, Biology, Physics 70 (2): 523–528.
Hering, B. J., M. Wijkstrom, and M. L. Graham, et al. 2006. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nature Medicine 12 (3): 301–303.
Hossain, P., B. Kawar, and M. El Nahas. 2007. Obesity and diabetes in the developing world—A growing challenge. The New England Journal of Medicine 356 (3): 213–215.
Kasimir, M. T., E. Rieder, and G. Seebacher, et al. 2006. Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves. Journal of Heart Valve Disease 15 (2): 278–286.
Kenyon, N. S., M. Chatzipetrou, and M. Masetti, et al. 1999. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proceedings of National Academy of Sciences United States of America 96 (14): 8132–8137.
Klymiuk, N., M. Muller, G. Brem, and B. Aigner. 2002. Characterization of porcine endogenous retrovirus gamma pro-pol nucleotide sequences. Journal of Virology 76 (22): 11738–11743.
Klymiuk, N., L. van Buerck, and A. Bähr, et al. 2012. Xenografted islet cell clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection. Diabetes. 61 (6):1527–1532.
Kouchoukos, N. T., E. H. Blackstone, F. L. Hanley, J. K. Kirlin, J. Kirklin, und B. Barratt-Boyes. 2012. Cardiac surgery. 4th ed. Churchill Livingstone, Elsevier, Oxford. 619–620.
Kuwaki, K., Y. L. Tseng, and F. J. Dor, et al. 2005. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors:Iinitial experience. Nature Medicine 11 (1): 29–31.
Le Tissier, P., J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss. 1997. Two sets of human-tropic pig retrovirus. Nature 389 (6652): 681–682.
Leveque, X., E. Cozzi, P. Naveilhan, and I. Neveu. 2011. Intracerebral xenotransplantation: Recent findings and perspectives for local immunosuppression. Current Opinion Organ Transplantation 16 (2): 190–194.
Ludwig, B., A. Rotem, and J. Schmid et al. 2012. Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proceedings of National Academy of Sciences United States of America 109 (13): 5022–5027.
Ludwig, B., A. Reichel, and A. Steffen et al. 2013. Transplantation of human islets without immunosuppression. Proceedings of National Academy of Sciences United States of America 110 (47): 19054–19058
McGregor, C. G., G. W. Byrne, and M. Vlasin, et al. 2009. Early cardiac function and gene expression after orthotopic cardiac xenotransplantation. Xenotransplantation 16: 356.
Meier-Kriesche, H. U., and B. Kaplan. 2002. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: A paired donor kidney analysis. Transplantation 74 (10): 1377–1381.
Mohiuddin, M. M., P. C. Corcoran, and A. K. Singh, et al. 2012. T-Cell depletion extends the survival of GTkO/hCD 46 Tg pig heart xenografts in baboons for up to 8 months. American Journal of Transplantation 12 (3): 763–771.
Mohiuddin, M. M., A. K. Singh, and P. C. Corcoran et al. 2014. Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation. The Journal of Thoracic and Cardiovascular Surgery 148 (3): 1106–1113.
Mueller, N. J., Y. Takeuchi, G. Mattiuzzo, and L. Scobie. 2011. Microbial safety in xenotransplantation. Current Opinion Organ Transplantation 16 (2): 201–206.
Nagata, H., R. Nishitai, and C. Shirota, et al. 2007. Prolonged survival of porcine hepatocytes in cynomolgus monkeys. Gastroenterology 132 (1): 321–329.
Oldmixon, B. A., J. C. Wood, and T. A. Ericsson, et al. 2002. Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine. Journal of Virology 76 (6): 3045–3048.
Palumbo, A., and K. Anderson. 2011. Multiple myeloma. The New England Journal of Medicine 364 (11): 1046–1060.
Petersen, B., W. Ramackers, and A. Tiede, et al. 2009. Pigs transgenic for human thrombomodulin have elevated production of activated protein C. Xenotransplantation 16 (6): 486–495.
Petersen, B., W. Ramackers, and A. Lucas-Hahn, et al. 2011. Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys. Xenotransplantation 18 (6): 355–368.
Phelps, C. J., C. Koike, and T. D. Vaught, et al. 2003. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 299 (5605): 411–414.
Pierson, R. N., III. 2009. Antibody-mediated xenograft injury: Mechanisms and protective strategies. Transplant Immunology 21: 65–69.
Rahmel, A. 2013. Eurotransplant International Foundation. Annual Report.
Ramirez, P., R. Chavez, and M. Majado, et al. 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.
Reichenspurner, H., P. A. Human, and D. H. Boehm, et al. 1989. Optimalization of immunosuppression after xenogeneic heart transplantation in primates. Journal of Heart Transplantation 8 (3): 200–207.
Roussel, J. C., C. J. Moran, and E. J. Salvaris, et al. 2008. Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI. American Journal of Transplantation 8 (6): 1101–1112.
Scobie, L., and Y. Takeuchi. 2009. Porcine endogenous retrovirus and other viruses in xenotransplantation. Current Opinion Organ Transplantation 14 (2): 175–179.
Shimizu, A., Y. Hisashi, and K. Kuwaki, et al. 2008. Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons. American Journal of Pathology 172 (6): 1471–1481.
Sun, Y., X. Ma, and D. Zhou, et al. 1996. Normalization of diabetes in spontaneously diabetic cynomologus monkeys by xenografts of microencapsulated porcine islets without immunosuppression. Journal of Clinical Investigation 98 (6): 1417–1422.
Van der Windt, D. J., R. Bottino, and A. Casu, et al. 2009. Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. American Journal of Transplantation 9 (12): 2716–2726.
WHO, First World Health Organization Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials: Changsha, China, 19–21 November 2008. The Changsha Communique. Xenotransplantation;16:61-3., and Second World Health Organization Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials: Geneva, Switzerland, 17-19 October 2011. http://www.who.int/transplantation/xeno/en/. Accessed 6 June 2015.WHO global consultations on regulatory requirements for xenotransplantation clinical trials. Changsha, China. November 19–21, 2008; Geneva, Switzerland, October 17–19, 2011. http://www.who.int/transplantation/xeno/en/.
Wolf, E. et al. Unpublished.
Wuensch, A., A. Baehr, and A. K. Bongoni et al. 2014. Regulatory sequences of the porcine THBD gene facilitate endothelial-specific expression of bioactive human thrombomodulin in single- and multitransgenic pigs. Transplantation 97 (2): 138–147.Wynyard, S., D. Nathu, O. Garkavenko, J. Denner J, and R. Elliott. 2014. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. Xenotransplantation 21 (4): 309–323.
Yamada, K., K. Yazawa, and A. Shimizu, et al. 2005. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nature Medicine 11 (1): 32–34.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Reichart, B. et al. (2016). Discordant Cellular and Organ Xenotransplantation—From Bench to Bedside. In: Jox, R., Assadi, G., Marckmann, G. (eds) Organ Transplantation in Times of Donor Shortage. International Library of Ethics, Law, and the New Medicine, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-319-16441-0_19
Download citation
DOI: https://doi.org/10.1007/978-3-319-16441-0_19
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-16440-3
Online ISBN: 978-3-319-16441-0
eBook Packages: Religion and PhilosophyPhilosophy and Religion (R0)