J Korean Soc Transplant.  2016 Jun;30(2):69-76. 10.4285/jkstn.2016.30.2.69.

Current Status of Solid Organ Xenotransplantation

Affiliations
  • 1Department of Surgery, Konkuk University School of Medicine, Seoul, Korea. ijyun@kuh.ac.kr

Abstract

Solid organ xenotransplantation using transgenic pig organs is proposed as an alternative method for allo-transplantation. To accomplish this, immunologic and non-immunologic barriers for xenotransplantation should be overcome, and experiments on pigs to non-human primates (NHP) are now ongoing for clinical application. Before the clinical experiment, public consensus about ethical decisions must be considered. The results of NHP experiments on solid organ xenotransplantation are improving, and it is expected that xeno-solid organs can be used as new organs for human patients in the future.

Keyword

Xenotransplantation; Solid organ transplantation; Transgenic pig

MeSH Terms

Consensus
Humans
Methods
Primates
Swine
Transplantation, Heterologous*

Reference

1). Taniguchi S., Cooper DK. Clinical xenotransplantation: past, present and future. Ann R Coll Surg Engl. 1997. 79:13–9.
2). Deschamps JY., Roux FA., Sai P. Gouin E. History of xenotransplantation. Xenotransplantation. 2005. 12:91–109.
3). Cooper DK., Ekser B., Tector AJ. A brief history of clinical xenotransplantation. Int J Surg. 2015. 23(Pt B):205–10.
Article
4). Bailey LL., Nehlsen-Cannarella SL., Concepcion W., Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA. 1985. 254:3321–9.
Article
5). Starzl TE., Fung J., Tzakis A., Todo S., Demetris AJ., Marino IR, et al. Baboon-to-human liver transplantation. Lancet. 1993. 341:65–71.
Article
6). Najarian JS. Experimental xenotransplantation: a personal history. Xenotransplantation. 2003. 10:10–5.
Article
7). Cooper DKC., Ezzelarab MB., Hara H., Iwase H., Lee W., Wijkstrom M, et al. The pathobiology of pig-to-primate xenotransplantation: a historical review. Xenotransplantation. 2016. 23:83–105.
Article
8). Roux FA., Saï P., Deschamps JY. Xenotransfusions, past and present. Xenotransplantation. 2007. 14:208–16.
Article
9). Gibson T. Zoografting: a curious chapter in the history of plastic surgery. Br J Plast Surg. 1995. 8:234–42.
Article
10). Hara H., Cooper DK. The immunology of corneal xenotransplantation: a review of the literature. Xenotransplantation. 2010. 17:338–49.
Article
11). Reemtsma K., McCracken BH., Schlegal JU., Pearl MA., Pearce CW., Dewitt CW, et al. Renal heterotransplantation in man. Ann Surg. 1964. 160:384–410.
Article
12). Hardy JD., Kurrus FD., Chavez CM., Neely WA., Eraslan S., Turner MD, et al. Heart transplantation in man. Developmental studies and report of a case. JAMA. 1964. 188:1132–40.
Article
13). Cooper DK., Gollackner B., Sachs DH. Will the pig solve the transplantation backlog? Ann Rev Med. 2002. 53:133–47.
Article
14). Lexer G., Cooper DK., Rose AG., Wicomb WN., Rees J., Keraan M, et al. Hyperacute rejection in an discordant (pig to baboon) cardiac xenograft model. J Heart Transplant. 1986. 5:411–8.
15). Cooper DK., Human PA., Lexer G., Rose AG., Rees J., Keraan M, et al. Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. J Heart Transplant. 1988. 7:238–46.
16). Phelps CJ., Koike C., Vaught TD., Boone J., Wells KD., Chen SH, et al. Production of alpha 1,3-galactosyltransferase-deficienct pigs. Science. 2003. 299:411–4.
17). Yamada K., Yazawa K., shimizu A., Iwanaga T., Hisashi Y., Nuhn M, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha 1,3-galactosyltransferase gene-knockout donors and the co-transplanplantation of vascularized thymic tissue. Nat Med. 2005. 11:32–4.
18). Iwase H., Kobayashi T. Current status of pig kidney xenotransplantation. Int J Surg. 2015. 23(Pt B):229–33.
Article
19). Cowan PJ., Robson SC., d'Apice AJ. Controlling coagulation dysregulation in xenotransplantation. Curr Opin Organ Transplant. 2011. 16:214–21.
Article
20). Cooper DK., Ekser B., Burlak C., Ezzelarab M., Hara H., Paris L, et al. Clinical lung xenotransplantation: what donor genetic modifications may be necessary? Xenotransplantation. 2012. 19:144–58.
21). Iwase H., Liu H., Wijkstrom M., Zhou H., Singh J., Hara H, et al. Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date. Xenotransplantation. 2015. 22:302–9.
22). Padler-Karavani V., Varki A. Poenial impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk. Xenotransplantation. 2011. 18:1–5.
23). Springer SA., Diaz SL., Gagneux P. Parallel evolution of a self-signal: humans and new would monkeys independently lost the cell surface sugar Neu5Gc. Immunogenetics. 2014. 66:671–4.
24). Mohiuddin MM., Singh AK., Corcoran PC., Hoyt RF., Thomas ML 3rd., Ayares D, et al. Genentically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation. J Thorac Cardiovasc Surg. 2014. 148:1106–13.
25). Chen G., Sun H., Yang H., Kubelik D., Garcia B., Luo Y, et al. 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. 2006. 81:273–83.
Article
26). Lee RS., Yamada K., Womer KL., Pillsbury EP., Allison KS., Marolew , et al. ski AE, Blockade of CD28-B7, but not CD40-CD154, prevents costimulation of allogeneic porcine and xenogeneic human anti-porcine T cell responses. J Immunol. 2000. 164:3434–44.
27). Iwase H., Ekser B., Satyananda V., Bhama J., Hara H., Ezzelarab M, et al. Pig-to-baboon heterotopic heart transplantation: exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens. Xenotranplantation. 2015. 22:211–20.
28). Lambrigts D., Sachs DH., Cooper DK. Discordant organ xenotransplantation in primates: world experience and current status. Transplantation. 1998. 66:547–61.
29). Cooper DK., Satyananda V., Ekser B., van der Windt DJ., Hara H., Ezzelarab MB, et al. Progress in pig-to-non-human primate transplantation models (1998-2013): a comprehensive review of the literature. Xenotransplantation. 2014. 21:397–419.
Article
30). Soin B., Smith KG., Zaidi A., Cozzi E., Bradley JR., Ostile DJ, et al. Physiological aspects of pig-to-primate renal xenotransplantation. Kindey Int. 2001. 60:1592–7.
Article
31). Ibrahim Z., Busch J., Awwad M., Wagner R., Wells K., Cooper DK. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems. Xenotransplantation. 2006. 13:488–99.
Article
32). Kim K., Schuetz C., Elias N., Veillette GR., Wamala I., Varma M, et al. Varma M. Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons. Xenotransplantation. 2012. 19:256–64.
33). Ekser B., Markmann JF., Tector AJ. Current status of pig liver xenotransplantation. Int J Surg. 2015. 23(Pt B):240–6.
Article
34). Kubicki N., Laird C., Burdorf L., Pierson RN 3rd., Azimzadeh AM. Current status of pig lung xenotransplantation. Int J Surg. 2015. (Pt B):);. 23:247–54.
Article
35). Sanchez PG., Bittle GJ., Burdorf L., Pierson RN 3rd., Griffith BP. State of art: clinical ex vivo lung perfusion: rationale, current status, and future directions. J Heart Lung Transplant. 2012. 31:339–48.
Article
36). Choi HJ., Lee JJ., Kim DH., Kim MK., Lee HJ., Ko AY, et al. Blockade of CD40-CD154 costimulatory pathway promotes long-term survival of full-thickness porcine corneal grafts in nonhuman primates: clinically applicable xenocorneal transplantation. Am J Transplant. 2015. 15:628–41.
Article
37). Choi HJ., Kim MK., Lee HJ., Ko JH., Jeong SH., Lee JI, et al. Efficacy of pig-to-rhesus lamellar corneal xenotransplantation. Invest Ophthalmol Vis Sci. 2011. 52:6643–50.
Article
38). Zhang MC., Liu X., Jin Y., Jiang DL., Wei XS., Xie HT. Lamellar keratoplasty treatment of fungal corneal ulcers with acellular porcine corneal stroma. Am J Transplant. 2015. 15:1068–75.
Article
39). Kim H., Chee HK., Yang J., Hwang S., Han KH., Kang J, et al. Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model. Transp Procc. 2013. 45:3085–91.
Article
40). Hwang S., Jung YD., Cho K., Ock SA., Oh KB., Kim HS, et al. No expression of porcine endogenous retrovirus after pig to monkey xenotransplantation. Lab Anim Res. 2014. 30:90–3.
Article
41). Sautermeister J., Mathieu R., Bogner V. Xenotransplantation-theological-ethical considerations in an interdisciplinary symposium. Xenotransplantation. 2015. 22:174–82.
Article
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