International Journal of Molecular Zoology 2024, Vol.14, No.2, 72-83 http://animalscipublisher.com/index.php/ijmz 81 The development of more targeted immunosuppressive therapies, as demonstrated by the prolonged survival of pig heart xenografts in baboons, also holds promise for improving clinical outcomes. Continued research is essential to refine genetic modifications and immunosuppressive protocols to ensure the long-term success of xenotransplantation. Researchers and clinicians must work together to address the remaining physiological and immunological challenges. Moreover, ethical considerations, including the welfare of genetically modified pigs and the potential risks to human recipients, must be carefully evaluated. Regulatory frameworks should be established to oversee the ethical and safe implementation of xenotransplantation in clinical practice. In conclusion, while significant progress has been made, ongoing research and ethical vigilance are crucial to realizing the full potential of xenotransplantation in addressing the organ shortage crisis. Acknowledgements The author extends sincere thanks to two anonymous peer reviewers for their invaluable feedback on the manuscript of this paper, whose critical evaluations and constructive suggestions have greatly contributed to the improvement of this manuscript. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Burdorf L., Laird C., Harris D., Connolly M., Habibabady Z., Redding E., O'Neill N., Cimeno A., Parsell D., Phelps C., Ayares D., Azimzadeh A., and Pierson R., 2021, Pig‐to‐baboon lung xenotransplantation: extended survival with targeted genetic modifications and pharmacologic treatments, American Journal of Transplantation, 22(1): 28-45. https://doi.org/10.1111/ajt.16809 PMid:34424601 PMCid:PMC10292947 Butler J., Wang Z., Martens G., Ladowski J., Li P., Tector M., and Tector A., 2016, Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response, Transplant immunology, 35: 47-51. https://doi.org/10.1016/j.trim.2016.02.001 PMid:26873419 Carvalho-Oliveira M., Valdivia E., Blasczyk R., and Figueiredo C., 2021, Immunogenetics of xenotransplantation, International Journal of Immunogenetics, 48(2): 120-134. https://doi.org/10.1111/iji.12526 PMid:33410582 Cooper D., Hara H., Iwase H., Yamamoto T., Li Q., Ezzelarab M., Federzoni E., Dandro A., and Ayares D., 2019, Justification of specific genetic modifications in pigs for clinical organ xenotransplantation, Xenotransplantation, 26(4): e12516. https://doi.org/10.1111/xen.12516 PMid:30989742 PMCid:PMC10154075 Eisenson D., Hisadome Y., and 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 PMid:35663933 PMCid:PMC9157571 Fischer K., Kraner-Scheiber S., Petersen B., Rieblinger B., Buermann A., Flisikowska T., Flisikowski K., Christan S., Edlinger M., Baars W., Kurome M., Zakhartchenko V., Kessler B., Plotzki E., Szczerbal I., Świtoński M., Denner J., Wolf E., Schwinzer R., Niemann H., Kind A., and Schnieke A., 2016, Efficient production of multi-modified pigs for xenotransplantation by ‘combineering’, gene stacking and gene editing, Scientific Reports, 6(1): 29081. https://doi.org/10.1038/srep29081 PMid:27353424 PMCid:PMC4926246 Fu R., Fang M., Xu K., Ren J., Zou J., Su L., Chen X., An P., Yu D., Ka M., Hai T., Li Z., Li W., Yang Y., Zhou Q., and Hu Z., 2020, Generation of GGTA1-/-β2M-/-CIITA-/-pigs using CRISPR/Cas9 technology to alleviate xenogeneic immune reactions, Transplantation, 104(8): 1566-1573. https://doi.org/10.1097/TP.0000000000003205 PMid:32732833 Hawthorne W., Salvaris E., Chew Y., Burns H., Hawkes J., Barlow H., Hu M., Lew A., Nottle M., O’Connell P., and Cowan P., 2022, Xenotransplantation of genetically modified neonatal pig islets cures diabetes in baboons, Frontiers in Immunology, 13: 898948. https://doi.org/10.3389/fimmu.2022.898948 PMid:35784286 PMCid:PMC9243461 Hryhorowicz M., Zeyland J., Słomski R., and Lipiński D., 2017, Genetically modified pigs as organ donors for xenotransplantation, Molecular Biotechnology, 59: 435-444. https://doi.org/10.1007/s12033-017-0024-9 PMid:28698981 PMCid:PMC5617878
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