Zwierzęta modyfikowane genetycznie jako źródła organów do ksenotransplantacji
DOI:
https://doi.org/10.12775/KOSMOS.2025.004Słowa kluczowe
ksenotransplantacja, transplantacje serca, transplantacja nerek, zwierzęta modyfikowane genetycznie, świnia, odrzucenie przeszczepuAbstrakt
Celem niniejszego artykułu jest przegląd danych literaturowych oraz podsumowanie aktualnego stanu wiedzy na temat zwierząt, które mogą stanowić potencjalne źródło narządów do ksentransplantacji. Ksenotransplantacja, rozumiana jako przeszczepianie tkanek lub narządów pomiędzy przedstawicielami różnych gatunków była przedmiotem badań od wielu lat. Pomimo rozważania innych gatunków jako potencjalnych dawców obecnie największe zainteresowanie budzi świnia (Sus domesticus), choć genetycznie różna od człowieka, wykazuje wiele cech sprzyjających temu zastosowaniu. Aby zminimalizować ryzyko odpowiedzi immunologicznej biorcy i odrzutu przeszczepu stosuje się modyfikacje genetyczne zwierząt. Rozwój technik genetyki molekularnej umożliwił szybkie i precyzyjne uzyskiwanie zmodyfikowanych zwierząt, których narządy są bardziej kompatybilne z ludzkim układem immunologicznym. Ksenotransplantacja postrzegana jest jako jedno z potencjalnych rozwiązań narastającego problemu niedoboru narządów do przeszczepów, związanego ze starzeniem się społeczeństw oraz wzrostem populacji. Praca ta analizuje zalety i ograniczenia ksenotransplantacji uwzględniając zarówno aspekty techniczne jaki i etyczne. Przedstawiono dotychczasowy rozwój tej dziedziny, w tym historie badań, potencjalne komplikacje związane z ksenoprzeszczepami, szczegóły dotyczące modyfikacji zwierząt oraz omówiono najnowsze osiągnięcia, w tym przeprowadzone już eksperymentalne przeszczepy u ludzi.
Bibliografia
Andrade G., AboHamza E., Elsantril Y., Ayoub A., Bedewy D. (2024). Moral approval of xenotransplantation in Egypt: associations with religion, attitudes towards animals and demographic factors. BMC Medical Ethics 25: 19. https://doi.org/10.1186/s12910-024-01013-3
Augier F., Salf E., Nottet J.B. (1996). [Dr. Samuel Serge Voronoff (1866-1951) or „the quest for eternal youth”]. Histoire des Sciences Médicales 30: 163–71.
Bailey L.L., Nehlsen-Cannarella S.L., Conception W., Jolley W.B. (1985). Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 254: 3321–29.
Barnard C.N., Wolpowitz A., Losman J.G. (1977). Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. South African Medical Journal 52: 1035–38.
Blusch J.H., Patience C., Martin U. (2002). Pig endogenous retroviruses and xenotransplantation. Xenotransplantation 9: 242–51. https://doi.org/10.1034/j.1399-3089.2002.01110.x
Borel J.F., Feurer C., Gubler H.U., Stähelin H. (1976). Biological effects of cyclosporin A: a new antilymphocytic agent. Agents and Actions 6: 468–75. https://doi.org/10.1007/BF01973261
Brink J.G., Hassoulas J. (2009). The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town – with reference to: the operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. Cardiovascular Journal of Africa 20: 31–35.
Bühler L., Basker M., Alwayn I.P., Goepfert C., Kitamura H., i in. (2000). Coagulation and thrombotic disorders associated with pig organ and hematopoietic cell transplantation in nonhuman primates. Transplantation 70: 1323–31. https://doi.org/10.1097/00007890-200011150-00010
Butler J.R., Paris L.L., Blankenship R.L., Sidner R.A., Martens G.R., i in. (2016). Silencing Porcine CMAH and GGTA1 Genes Significantly Reduces Xenogeneic Consumption of Human Platelets by Porcine Livers. Transplantation 100: 571–76. https://doi.org/10.1097/TP.0000000000001071
Byrne G.W., Stalboerger P.G., Davila E., Heppelmann C.J., Gazi M.H., i in. (2008). Proteomic identification of non-Gal antibody targets after pig-to-primate cardiac xenotransplantation. Xenotransplantation 15: 268–76. https://doi.org/10.1111/j.1399-3089.2008.00480.x
Calne R.Y., White H.J., Herbertson B.M., Millard P.R., Davis D.R., i in. (1968). Pig-to-baboon liver xenografts. Lancet 1: 1176–78. https://doi.org/10.1016/s0140-6736(68)91869-2
Cantu E., Balsara K.R., Li B., Lau C., Gibson S., i in. (2007). Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts. American Journal of Transplantation 7: 66–75. https://doi.org/10.1111/j.1600-6143.2006.01603.x
Chen G., Qian H., Starzl T., Sun H., Garcia B., i in. (2005). Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nature Medicine 11: 1295–98. https://doi.org/10.1038/nm1330
Cleveland J.D., Mitchell C., Cooper D.K.C., Cleveland D.C. (2023). The potential of cardiac xenotransplantation for management of infants with complex congenital heart disease. Translational Pediatrics 12: 2247–55. https://doi.org/10.21037/tp-22-664
Cooper D.K.C. (2021). Genetically engineered pig kidney transplantation in a brain-dead human subject. Xenotransplantation 28: e12718. https://doi.org/10.1111/xen.12718
Cooper D.K.C., Ekser B., Tector A.J. (2015). Immunobiological barriers to xenotransplantation. International Journal of Surgery 23: 211–16. https://doi.org/10.1016/j.ijsu.2015.06.068
Cooper D.K.C., Gaston R., Eckhoff D., Ladowski J., Yamamoto T., i in. (2018). Xenotransplantation-the current status and prospects. British Medical Bulletin 125: 5–14. https://doi.org/10.1093/bmb/ldx043
Cooper D.K.C., Human P.A., Lexer G., Rose A.G., Rees J., i in. (1988). Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. Journal of Heart Transplantation 7: 238–46.
Cope Z. (1967). Safavid Surgery. Proceedings of the Royal Society of Medicine 60: 107. https://doi.org/10.1177/003591576706000156
Cowan P.J., d'Apice A.J.F. (2009). Complement activation and coagulation in xenotransplantation. Immunology and Cell Biology 87: 203–8. https://doi.org/10.1038/icb.2008.107
Cowan P.J., Cooper D.K.C., d'Apice A.J.F. (2014). Kidney xenotransplantation. Kidney International 85: 265–75. https://doi.org/10.1038/ki.2013.381
Czaplicki J., Blońska B., Religa Z. (1992). The lack of hyperacute xenogeneic heart transplant rejection in a human. Journal of Heart and Lung Transplantation 11: 393–97.
Daar A.S. (1997). Ethics of xenotransplantation: animal issues, consent, and likely transformation of transplant ethics. World Journal of Surgery 21: 975–82. https://doi.org/10.1007/s002689900336
Denner J. (2021). Porcine Endogenous Retroviruses and Xenotransplantation, 2021. Viruses 13: 2156. https://doi.org/10.3390/v13112156
Denner J. (2008). Recombinant porcine endogenous retroviruses (PERV-A/C): a new risk for xenotransplantation? Archives of Virology 153: 1421–26. https://doi.org/10.1007/s00705-008-0141-7
Deschamps J.-Y., Roux F.A., Saï P., Gouin E. (2005). History of xenotransplantation. Xenotransplantation 12: 91–109. https://doi.org/10.1111/j.1399-3089.2004.00199.x
Eisenson D.L., Hisadome Y., Yamada K. (2022). Progress in Xenotransplantation: Immunologic Barriers, Advances in Gene Editing, and Successful Tolerance Induction Strategies in Pig-To-Primate Transplantation. Frontiers in Immunology 13: 899657. https://doi.org/10.3389/fimmu.2022.899657
Ekser B., Bianchi J., Ball S., Iwase H., Walters A., i in. (2012). Comparison of hematologic, biochemical, and coagulation parameters in α1,3-galactosyltransferase gene-knockout pigs, wild-type pigs, and four primate species. Xenotransplantation 19: 342–54. https://doi.org/10.1111/xen.12007
Ericsson T., Oldmixon B., Blomberg J., Rosa M., Patience C., i in. (2001). Identification of novel porcine endogenous betaretrovirus sequences in miniature swine. Journal of Virology 75: 2765–70. https://doi.org/10.1128/JVI.75.6.2765-2770.2001
Farr A.D. (1980). The first human blood transfusion. Medical History 24: 143–62. https://doi.org/10.1017/s0025727300040138
Fernández-Ruiz I. (2019). Breakthrough in heart xenotransplantation. Nature Reviews Cardiology 16: 69. https://doi.org/10.1038/s41569-018-0151-4
Fiebig U., Fischer K., Bähr A., Runge C., Schnieke A., i in. (2018). Porcine endogenous retroviruses: Quantification of the copy number in cell lines, pig breeds, and organs. Xenotransplantation 25: e12445. https://doi.org/10.1111/xen.12445
Fishman J.A. (2019). Infection in xenotransplantation: opportunities and challenges. Current Opinion in Organ Transplantation 24: 527–34. https://doi.org/10.1097/MOT.0000000000000682
Fishman J.A., Scobie L., Takeuchi Y. (2012). Xenotransplantation-associated infectious risk: a WHO consultation. Xenotransplantation 19: 72–81. https://doi.org/10.1111/j.1399-3089.2012.00693.x
Furie B., Furie B.C. (2008). Mechanisms of thrombus formation. New England Journal of Medicine 359: 938–49. https://doi.org/10.1056/NEJMra0801082
Galili U. (1993). Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunology Today 14: 480–82. https://doi.org/10.1016/0167-5699(93)90261-i
Galili U., Shohet S.B., Kobrin E., Stults C.L., Macher B.A. (1988). Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. Journal of Biological Chemistry 263: 17755–62.
Galvao F.H.F., Grinberg M. (2023). Bioethics and xenotransplantation from pig to human. Clinics (Sao Paulo, Brazil) 78: 100170. https://doi.org/10.1016/j.clinsp.2023.100170
Godehardt A.W., Fischer N., Rauch P., Gulich B., Boller K., i in. (2020). Characterization of porcine endogenous retrovirus particles released by the CRISPR/Cas9 inactivated cell line PK15 clone 15. Xenotransplantation 27: e12563. https://doi.org/10.1111/xen.12563
Goerlich C.E., Griffith B., Hanna P., Hong S.N., Ayares D., i in. (2023). The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors. Journal of Thoracic and Cardiovascular Surgery 165: e69–81. https://doi.org/10.1016/j.jtcvs.2021.07.051
Gollackner B., Goh S.K., Qawi I., Buhler L., Knosalla C., i in. (2004). Acute vascular rejection of xenografts: roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity. Transplantation 77: 1735–41. https://doi.org/10.1097/01.tp.0000131167.21930.b8
Gorer P.A., Loutit J.F., Micklem H.S. (1961). Proposed revisions of „transplantese”. Nature 189: 1024–25. https://doi.org/10.1038/1891024a0
Griffith B.P., Goerlich C.E., Singh A.K., Rothblatt M., Lau C.L., i in. (2022). Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. New England Journal of Medicine 387: 35–44. https://doi.org/10.1056/NEJMoa2201422
Griffith B.P., Grazioli A., Singh A.K., Tully A., Galindo J., i in. (2025). Transplantation of a genetically modified porcine heart into a live human. Nature Medicine 31: 589–98. https://doi.org/10.1038/s41591-024-03429-1
Haeseker B. (1991). Van Meekeren and his account of the transplant of bone from a dog into the skull of a soldier. Plastic and Reconstructive Surgery 88: 173–74.
Hansen-Estruch C., Cooper D.K.C., Judd E. (2022). Physiological aspects of pig kidney xenotransplantation and implications for management following transplant. Xenotransplantation 29: e12743. https://doi.org/10.1111/xen.12743
Harris D.G., Quinn K.J., French B.M., Schwartz E., Kang E., i in. (2015). Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood. Xenotransplantation 22: 102–11. https://doi.org/10.1111/xen.12149
Hawthorne W.J., Cowan P.J., Bühler L.H., Yi S., Bottino R., i in. (2019). Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, Changsha, Hunan, China December 12-14, 2018: „The 2018 Changsha Communiqué” The 10-Year Anniversary of The International Consultation on Xenotransplantation. Xenotransplantation 26: e12513. https://doi.org/10.1111/xen.12513
Hirose T., Ma D., Lassiter G., Sasaki H., Rosales I., i in. (2021). Successful Long-Term TMA- and Rejection-Free Survival of a Kidney Xenograft With Triple Xenoantigen Knockout Plus Insertion of Multiple Human Transgenes. American Journal of Transplantation 21: 477–477.
Hurst D.J., Ali M., Brown S.M., Gielen J., Kashyap K., i in. (2025). Religious Perspectives Regarding the Ethical Issues Associated With Clinical Xenotransplantation. Xenotransplantation 32: e70036. https://doi.org/10.1111/xen.70036
Ide K., Wang H., Tahara H., Liu J., Wang X., i in. (2007). Role for CD47-SIRPalpha signaling in xenograft rejection by macrophages. Proceedings of the National Academy of Sciences of the United States of America 104: 5062–66. https://doi.org/10.1073/pnas.0609661104
Iwase H., Ekser B., Hara H., Phelps C., Ayares D., i in. (2014). Regulation of human platelet aggregation by genetically modified pig endothelial cells and thrombin inhibition. Xenotransplantation 21: 72–83. https://doi.org/10.1111/xen.12073
Iwase H., Klein E.C., Cooper D.K. (2018). Physiologic Aspects of Pig Kidney Transplantation in Nonhuman Primates. Comparative Medicine 68: 332–40. https://doi.org/10.30802/AALAS-CM-17-000117
Kaur G., Thompson L., Dufour J. (2015). Therapeutic potential of immune privileged Sertoli cells. Animal Reproduction 12: 105–17.
Keys T.E. (1973). Dr. Paul Bert (1833–1886). Anesthesia and Analgesia 52: 437–38.
Kobayashi T., Taniguchi S., Neethling F.A., Rose A.G., Hancock W.W., i in. (1997). Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy. Transplantation 64: 1255–61. https://doi.org/10.1097/00007890-199711150-00005
Kupiec-Węgliński J.W. (2022). Grand Challenges in Organ Transplantation. Frontiers in Transplantation 1: 897679. https://doi.org/10.3389/frtra.2022.897679
Kuss R., Bourget P. (1992). An Illustrated History of Organ Transplantation: The Great Adventure of the Century. Sandoz.
Lau C.L., Cantu E., Gonzalez-Stawinski G.V., Holzknecht Z.E., Nichols T.C., i in. (2003). The role of antibodies and von Willebrand factor in discordant pulmonary xenotransplantation. American Journal of Transplantation 3: 1065–75. https://doi.org/10.1034/j.1600-6143.2003.00190.x
Lin C.C., Ezzelarab M., Hara H., Long C., Lin C.W., i in. (2010). Atorvastatin or transgenic expression of TFPI inhibits coagulation initiated by anti-nonGal IgG binding to porcine aortic endothelial cells. Journal of Thrombosis and Haemostasis 8: 2001–10. https://doi.org/10.1111/j.1538-7836.2010.03950.x
Mallapaty S., Kozlov M. (2025). The science behind the first pig-organ transplant trial in humans. Nature 638: 303–4. https://doi.org/10.1038/d41586-025-00368-w
Martin C., Plat M., Nerrière-Daguin V., Coulon F., Uzbekova S., i in. (2005). Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Research 14: 373–84. https://doi.org/10.1007/s11248-004-7268-4
Matsumoto S., Asari S., Nanno Y., Nakamura H., Okawa T., i in. (2025). Donor pigs for clinical islet xenotransplantation: Review and future directions. Cell Transplantation 34: 9636897251332532. https://doi.org/10.1177/09636897251332532
McLoughlin G. (1959). The British Contribution to Blood Transfusion in the 19th-Century. British Journal of Anaesthesia 31: 503–16. https://doi.org/10.1093/bja/31.11.503
Meier R.P.H., Longchamp A., Mohiuddin M., Manuel O., Vrakas G., i in. (2021). Recent progress and remaining hurdles toward clinical xenotransplantation. Xenotransplantation 28: e12681. https://doi.org/10.1111/xen.12681
Miwa Y., Yamamoto K., Onishi A., Iwamoto M., Yazaki S., i in. (2010). Potential value of human thrombomodulin and DAF expression for coagulation control in pig-to-human xenotransplantation. Xenotransplantation 17: 26–37. https://doi.org/10.1111/j.1399-3089.2009.00555.x
Mohiuddin M.M., Singh A.K., Corcoran P.C., Thomas Iii M.L., Clark T., i in. (2016). Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nature Communications 7: 11138. https://doi.org/10.1038/ncomms11138
Mueller N.J., Kuwaki K., Dor F.J.M.F., Knosalla C., Gollackner B., i in. (2004a). Reduction of consumptive coagulopathy using porcine cytomegalovirus-free cardiac porcine grafts in pig-to-primate xenotransplantation. Transplantation 78: 1449–53. https://doi.org/10.1097/01.tp.0000141361.68446.1f
Mueller N.J., Livingston C., Knosalla C., Barth R.N., Yamamoto S., i in. (2004b). Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation. Journal of Infectious Diseases 189: 1628–33. https://doi.org/10.1086/383351
Niu D., Wei H.-J., Lin L., George H., Wang T., i in. (2017). Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science 357: 1303–7. https://doi.org/10.1126/science.aan4187
Park J.-K., Lee Y.-K., Lee P., Chung H.-J., Kim S., i in. (2006). Recombinant human erythropoietin produced in milk of transgenic pigs. Journal of Biotechnology 122: 362–71. https://doi.org/10.1016/j.jbiotec.2005.11.021
Patel M.S., Louras N., Vagefi P.A. (2017). Liver xenotransplantation. Current Opinion in Organ Transplantation 22: 535–40. https://doi.org/10.1097/MOT.0000000000000459
Pierson R.N., Dorling A., Ayares D., Rees M.A., Seebach J.D., i in. (2009). Current status of xenotransplantation and prospects for clinical application. Xenotransplantation 16: 263–80. https://doi.org/10.1111/j.1399-3089.2009.00534.x
Porrett P.M., Orandi B.J., Kumar V., Houp J., Anderson D., i in. (2022). First clinical-grade porcine kidney xenotransplant using a human decedent model. American Journal of Transplantation 22: 1037–53. https://doi.org/10.1111/ajt.16930
Pouyet M., Berard P. (1971). [2 cases of true heterotopic transplantation of the baboon liver in malignant acute hepatitis]. Lyon Chir. 67: 288–91.
Ramsoondar J., Vaught T., Ball S., Mendicino M., Monahan J., i in. (2009). Production of transgenic pigs that express porcine endogenous retrovirus small interfering RNAs. Xenotransplantation 16: 164–80. https://doi.org/10.1111/j.1399-3089.2009.00525.x
Ray P., Gupta N.H., Roy M. (1980). Sushruta Samhita A Scientific Synopsis.
Reyes L.M., Estrada J.L., Wang Z.Y., Blosser R.J., Smith R.F., i in. (2014). Creating class I MHC-null pigs using guide RNA and the Cas9 endonuclease. Journal of Immunology 193: 5751–57. https://doi.org/10.4049/jimmunol.1402059
Rinaldi E. (1987). The first homoplastic limb transplant according to the legend of Saint Cosmas and Saint Damian. Italian Journal of Orthopaedics and Traumatology 13: 393–406.
Rollin B.E. (2020). Ethical and Societal Issues Occasioned by Xenotransplantation. Animals 10: 1695. https://doi.org/10.3390/ani10091695
Roussel J.C., Moran C.J., Salvaris E.J., Nandurkar H.H., d'Apice A.J.F., i in. (2008). Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI. American Journal of Transplantation 8: 1101–12. https://doi.org/10.1111/j.1600-6143.2008.02210.x
Schultheiss D., Denil J., Jonas U. (1997). Rejuvenation in the early 20th century. Andrologia 29: 351–55. https://doi.org/10.1111/j.1439-0272.1997.tb00329.x
Schuurman H.-J., Cheng J., Lam T. (2003). Pathology of xenograft rejection: a commentary. Xenotransplantation 10: 293–99. https://doi.org/10.1034/j.1399-3089.2003.02092.x
Singh A.K., Chan J.L., DiChiacchio L., Hardy N.L., Corcoran P.C., i in. (2019). Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs. Xenotransplantation 26: e12465. https://doi.org/10.1111/xen.12465
Smood B., Hara H., Schoel L.J., Cooper D.K.C. (2019). Genetically-engineered pigs as sources for clinical red blood cell transfusion: What pathobiological barriers need to be overcome? Blood Reviews 35: 7–17. https://doi.org/10.1016/j.blre.2019.01.003
Starzl T.E., Fung J., Tzakis A., Todo S., Demetris A.J., i in. (1993). Baboon-to-human liver transplantation. Lancet 341: 65–71. https://doi.org/10.1016/0140-6736(93)92553-6
Starzl T.E., Valdivia L.A., Murase N., Demetris A.J., Fontes P., i in. (1994). The biological basis of and strategies for clinical xenotransplantation. Immunological Reviews 141: 213–44. https://doi.org/10.1111/j.1600-065x.1994.tb00879.x
Sykes M., Sachs D.H. (2019). Transplanting organs from pigs to humans. Science Immunology 4: eaau6298. https://doi.org/10.1126/sciimmunol.aau6298
Tena A., Kurtz J., Leonard D.A., Dobrinsky J.R., Terlouw S.L., i in. (2014). Transgenic expression of human CD47 markedly increases engraftment in a murine model of pig-to-human hematopoietic cell transplantation. American Journal of Transplantation 14: 2713–22. https://doi.org/10.1111/ajt.12918
Tönjes R.R., Niebert M. (2003). Relative age of proviral porcine endogenous retrovirus sequences in Sus scrofa based on the molecular clock hypothesis. Journal of Virology 77: 12363–68. https://doi.org/10.1128/jvi.77.22.12363-12368.2003
Wang Y., Yang H.-Q., Jiang W., Fan N.-N., Zhao B.-T., i in. (2015). Transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) by porcine skin for xenogeneic skin grafting. Transgenic Research 24: 199–211. https://doi.org/10.1007/s11248-014-9833-9
Warty V., Diven W., Cadoff E., Todo S., Starzl T., i in. (1988). FK506: a novel immunosuppressive agent. Characteristics of binding and uptake by human lymphocytes. Transplantation 46: 453–55. https://doi.org/10.1097/00007890-198809000-00025
Wheeler D.G., Joseph M.E., Mahamud S.D., Aurand W.L., Mohler P.J., i in. (2012). Transgenic swine: expression of human CD39 protects against myocardial injury. Journal of Molecular and Cellular Cardiology 52: 958–61. https://doi.org/10.1016/j.yjmcc.2012.01.002
Yan J.-J., Koo T.Y., Lee H.-S., Lee W.-B., Kang B., i in. (2018). Role of Human CD200 Overexpression in Pig-to-Human Xenogeneic Immune Response Compared With Human CD47 Overexpression. Transplantation 102: 406–16. https://doi.org/10.1097/TP.0000000000001966
Yang L., Güell M., Niu D., George H., Lesha E., i in. (2015). Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science 350: 1101–4. https://doi.org/10.1126/science.aad1191
Zhang R., Wang Y., Chen L., Wang R., Li C., i in. (2018). Reducing immunoreactivity of porcine bioprosthetic heart valves by genetically-deleting three major glycan antigens, CGTA1/β4GalNT2/CMAH. Acta Biomaterialia 72: 196–205. https://doi.org/10.1016/j.actbio.2018.03.055
Zhou Q., Li T., Wang K., Zhang Q., Geng Z., i in. (2022). Current status of xenotransplantation research and the strategies for preventing xenograft rejection. Frontiers in Immunology 13: 928173. https://doi.org/10.3389/fimmu.2022.928173
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