Current status of xenotransplantation from an immunobiological standpoint

Xenotransplantation, which involves the transplantation of organs, tissues, or cells from animals into humans, is emerging as a promising solution to mitigate the global shortage of human donor organs. Nonetheless, its clinical application is constrained by significant immunological and physiologica...

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Main Authors: Jaecheon Ko, Geon Lee, Hyun Woo Kim, Minji Kang, Hyun Je Kim, Chung-Gyu Park
Format: Article
Language:English
Published: The Korean Society for Transplantation 2025-06-01
Series:Clinical Transplantation and Research
Subjects:
Online Access:https://www.ctrjournal.org/journal/view.html?doi=10.4285/ctr.24.0065
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author Jaecheon Ko
Geon Lee
Hyun Woo Kim
Minji Kang
Hyun Je Kim
Chung-Gyu Park
author_facet Jaecheon Ko
Geon Lee
Hyun Woo Kim
Minji Kang
Hyun Je Kim
Chung-Gyu Park
author_sort Jaecheon Ko
collection DOAJ
description Xenotransplantation, which involves the transplantation of organs, tissues, or cells from animals into humans, is emerging as a promising solution to mitigate the global shortage of human donor organs. Nonetheless, its clinical application is constrained by significant immunological and physiological barriers—most notably, the rapid rejection of xenografts by both the innate and adaptive immune systems. This review discusses critical immunological challenges such as natural antibodies, complement activation, coagulation dysregulation, and cellular immune responses mediated by T cells, macrophages, and natural killer cells. Advances in genetic engineering—such as the development of multi-knockout pigs that lack major xenoantigens and the transgenic expression of human regulatory proteins—have considerably prolonged xenograft survival in preclinical models. Moreover, approaches such as mixed hematopoietic chimerism, thymic transplantation, cell-based therapies, and synthetic particle-based delivery hold promise for inducing immune tolerance. Innovations in pharmacological immunosuppression and bioengineering, including islet encapsulation and thrombo-regulatory modifications, further enhance graft viability. While recent breakthroughs, including pig-to-human transplants, demonstrate considerable clinical potential, challenges remain in achieving long-term graft survival. This review summarizes current progress in xenotransplantation research and outlines future directions to overcome cross-species immune barriers, bringing the field closer to widespread clinical application.
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institution Kabale University
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publishDate 2025-06-01
publisher The Korean Society for Transplantation
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series Clinical Transplantation and Research
spelling doaj-art-41de1ec783fd432289c06278e91f7b2a2025-08-20T03:27:46ZengThe Korean Society for TransplantationClinical Transplantation and Research3022-67832025-06-013929711510.4285/ctr.24.0065ctr.24.0065Current status of xenotransplantation from an immunobiological standpointJaecheon Ko0Geon Lee1Hyun Woo Kim2Minji Kang3Hyun Je Kim4Chung-Gyu Park5Transplantation Research Institute, Seoul National University College of Medicine, Seoul, KoreaTransplantation Research Institute, Seoul National University College of Medicine, Seoul, KoreaDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, KoreaDepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul, KoreaTransplantation Research Institute, Seoul National University College of Medicine, Seoul, KoreaTransplantation Research Institute, Seoul National University College of Medicine, Seoul, KoreaXenotransplantation, which involves the transplantation of organs, tissues, or cells from animals into humans, is emerging as a promising solution to mitigate the global shortage of human donor organs. Nonetheless, its clinical application is constrained by significant immunological and physiological barriers—most notably, the rapid rejection of xenografts by both the innate and adaptive immune systems. This review discusses critical immunological challenges such as natural antibodies, complement activation, coagulation dysregulation, and cellular immune responses mediated by T cells, macrophages, and natural killer cells. Advances in genetic engineering—such as the development of multi-knockout pigs that lack major xenoantigens and the transgenic expression of human regulatory proteins—have considerably prolonged xenograft survival in preclinical models. Moreover, approaches such as mixed hematopoietic chimerism, thymic transplantation, cell-based therapies, and synthetic particle-based delivery hold promise for inducing immune tolerance. Innovations in pharmacological immunosuppression and bioengineering, including islet encapsulation and thrombo-regulatory modifications, further enhance graft viability. While recent breakthroughs, including pig-to-human transplants, demonstrate considerable clinical potential, challenges remain in achieving long-term graft survival. This review summarizes current progress in xenotransplantation research and outlines future directions to overcome cross-species immune barriers, bringing the field closer to widespread clinical application.https://www.ctrjournal.org/journal/view.html?doi=10.4285/ctr.24.0065xenotransplantationimmune barriersgenetic engineeringorgan transplantationimmune tolerance
spellingShingle Jaecheon Ko
Geon Lee
Hyun Woo Kim
Minji Kang
Hyun Je Kim
Chung-Gyu Park
Current status of xenotransplantation from an immunobiological standpoint
Clinical Transplantation and Research
xenotransplantation
immune barriers
genetic engineering
organ transplantation
immune tolerance
title Current status of xenotransplantation from an immunobiological standpoint
title_full Current status of xenotransplantation from an immunobiological standpoint
title_fullStr Current status of xenotransplantation from an immunobiological standpoint
title_full_unstemmed Current status of xenotransplantation from an immunobiological standpoint
title_short Current status of xenotransplantation from an immunobiological standpoint
title_sort current status of xenotransplantation from an immunobiological standpoint
topic xenotransplantation
immune barriers
genetic engineering
organ transplantation
immune tolerance
url https://www.ctrjournal.org/journal/view.html?doi=10.4285/ctr.24.0065
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AT minjikang currentstatusofxenotransplantationfromanimmunobiologicalstandpoint
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