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      Advancing kidney xenotransplantation with anesthesia and surgery - bridging preclinical and clinical frontiers challenges and prospects

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          Abstract

          Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and formulating effective immunosuppressive protocols crucial for transplant success. Critical to advancing xenotransplantation into clinical settings are the nuanced considerations of anesthesia and surgical practices required for these complex procedures. The precise genetic modification of porcine kidneys marks a significant leap in addressing the biological and immunological hurdles that have traditionally challenged xenotransplantation. Yet, the success of these transplants hinges on the process of meticulously matching these organs with human recipients, which demands thorough understanding of immunological compatibility, the risk of organ rejection, and the prevention of zoonotic disease transmission. In parallel, the development and optimization of immunosuppressive protocols are imperative to mitigate rejection risks while minimizing side effects, necessitating innovative approaches in both pharmacology and clinical practices. Furthermore, the post-operative care of recipients, encompassing vigilant monitoring for signs of organ rejection, infectious disease surveillance, and psychological support, is crucial for ensuring post-transplant life quality. This comprehensive care highlights the importance of a multidisciplinary approach involving transplant surgeons, anesthesiologists, immunologists, infectiologists and psychiatrists. The integration of anesthesia and surgical expertise is particularly vital, ensuring the best possible outcomes of those patients undergoing these novel transplants, through safe procedural practices. As xenotransplantation moving closer to clinical reality, establishing consensus guidelines on various aspects, including donor-recipient selection, immunosuppression, as well as surgical and anesthetic management of these transplants, is essential. Addressing these challenges through rigorous research and collective collaboration will be the key, not only to navigate the ethical, medical, and logistical complexities of introducing kidney xenotransplantation into mainstream clinical practice, but also itself marks a new era in organ transplantation.

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          Most cited references31

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          Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

          Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.
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            Importance of the pig as a human biomedical model

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              Long-Term Survival after Kidney Transplantation

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                Author and article information

                Contributors
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                URI : https://loop.frontiersin.org/people/2662353Role:
                URI : https://loop.frontiersin.org/people/2661467Role:
                URI : https://loop.frontiersin.org/people/2668962Role:
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                URI : https://loop.frontiersin.org/people/1881455Role:
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                22 March 2024
                2024
                : 15
                : 1386382
                Affiliations
                [1] 1 Central of Reproductive Medicine, Department of Obstetrics and Gynecology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China , Chengdu, China
                [2] 2 Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China , Chengdu, China
                [3] 3 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University , Wuhan, China
                [4] 4 Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine , Standford, CA, United States
                [5] 5 The First Clinical Medical College of Norman Bethune University of Medical Sciences , Jilin, China
                [6] 6 Eye Center, Renmin Hospital of Wuhan University, Wuhan University , Wuhan, Hubei, China
                [7] 7 Department of Geriatrics, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences , Little Rock, AR, United States
                [8] 8 Department of Neuroscience, Baylor College of Medicine , Houston, TX, United States
                [9] 9 School of Pharmacy, Guangxi University of Chinese Medicine , Nanning, China
                Author notes

                Edited by: Lisha Mou, Shenzhen Second People’s Hospital, China

                Reviewed by: Dafei Chai, Xuzhou Medical University, China

                Rongkai Yan, The Ohio State University, United States

                *Correspondence: Yi Wang, w_yi2022@ 123456163.com ; Jianzhen Lv, cancan912@ 123456163.com ; Si-Yuan Song, si-yuan.song@ 123456bcm.edu

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2024.1386382
                10998442
                38585270
                ccd93d91-2c1b-4ebd-a6bf-fbbe02acff4c
                Copyright © 2024 Zhang, Wang, Xie, Zhang, Yang, Yuan, Cui, Song, Lv and Wang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 February 2024
                : 13 March 2024
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 31, Pages: 7, Words: 3027
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Natural Science Foundation of China (81802504), grants from the Sichuan Science and Technology Bureau (20211YFH0384 and 2023YFH0010), and a grant from Guangxi Natural Science Foundation (2022GXNSFAA035608).
                Categories
                Immunology
                Mini Review
                Custom metadata
                Alloimmunity and Transplantation

                Immunology
                xenogeneic kidney transplantation,genetically modified pigs,anesthesia,immunological compatibility,organ rejection,immunotherapy,surgical techniques

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