دورية أكاديمية
First clinical-grade porcine kidney xenotransplant using a human decedent model.
| العنوان: | First clinical-grade porcine kidney xenotransplant using a human decedent model. |
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| المؤلفون: | Porrett PM; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Orandi BJ; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Kumar V; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Houp J; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Anderson D; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Cozette Killian A; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Hauptfeld-Dolejsek V; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Martin DE; Deakin University School of Medicine, Geelong, Victoria, Australia., Macedon S; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Budd N; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Stegner KL; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Dandro A; Revivicor, Inc, Blacksburg, Virginia, USA., Kokkinaki M; Revivicor, Inc, Blacksburg, Virginia, USA., Kuravi KV; Revivicor, Inc, Blacksburg, Virginia, USA., Reed RD; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Fatima H; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Killian JT Jr; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Baker G; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Perry J; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Wright ED; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Cheung MD; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Erman EN; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Kraebber K; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Gamblin T; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Guy L; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., George JF; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA., Ayares D; Revivicor, Inc, Blacksburg, Virginia, USA., Locke JE; University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA. |
| المصدر: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Apr; Vol. 22 (4), pp. 1037-1053. Date of Electronic Publication: 2022 Jan 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 100968638 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-6143 (Electronic) Linking ISSN: 16006135 NLM ISO Abbreviation: Am J Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Original Publication: Copenhagen : Munksgaard International Publishers, 2001- |
| مواضيع طبية MeSH: | Graft Rejection*/pathology , Kidney*, Animals ; Animals, Genetically Modified ; Heterografts ; Humans ; Prospective Studies ; Swine ; Transplantation, Heterologous |
| مستخلص: | A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre-clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain-dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation. The decedent was hemodynamically stable through reperfusion, and vascular integrity was maintained despite the exposure of the xenografts to human blood pressure. No hyperacute rejection was observed, and the kidneys remained viable until termination 74 h later. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown. In summary, our study suggests that major barriers to human xenotransplantation have been surmounted and identifies where new knowledge is needed to optimize xenotransplantation outcomes in humans. (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.) |
| التعليقات: | Comment in: Am J Transplant. 2022 Apr;22(4):1007-1008. (PMID: 35073605) Comment in: Nat Rev Nephrol. 2022 Apr;18(4):199. (PMID: 35132215) Comment in: Am J Transplant. 2022 Jul;22(7):1935-1936. (PMID: 35213783) Comment in: Am J Transplant. 2022 Apr;22(4):1003-1004. (PMID: 35373525) Comment in: Xenotransplantation. 2022 May;29(3):e12748. (PMID: 35616243) |
| References: | System USRD. 2020 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2020. Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725-1730. Goldberg DS, Abt PL, Blumberg EA, et al. Trial of Transplantation of HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;376:2394-2395. Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011;365:318-326. Starzl TE, Marchioro TL, Peters GN, et al. Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation. 1964;2:752-776. Sykes M, Sachs DH. Transplanting organs from pigs to humans. Sci Immunol. 2019;4(41):eaau6298. Kuwaki K, Tseng YL, Dor FJ, et al. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005;11:29-31. Phelps CJ, Koike C, Vaught TD, et al. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science. 2003;299:411-414. Yamada K, Yazawa K, Shimizu A, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005;11:32-34. Cooper DKC, Hara H, Iwase H, et al. Justification of specific genetic modifications in pigs for clinical organ xenotransplantation. Xenotransplantation. 2019;26:e12516. Eyestone W, Adams K, Ball S, et al. Gene edited pigs for xenotransplantation. In: Cooper DKC, Byrne G, eds. Clinical Xenotransplantation. Springer International Publishing; 2020. Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science. 2017;357:1303-1307. Yang L, Guell M, Niu D, et al. Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science. 2015;350:1101-1104. Parent B, Gelb B, Latham S, et al. The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects. J Med Ethics. 2020;46:199-204. Wood KE, Becker BN, McCartney JG, D'Alessandro AM, Coursin DB. Care of the potential organ donor. N Engl J Med. 2004;351:2730-2739. Yamamoto T, Hara H, Foote J, et al. Life-supporting kidney xenotransplantation from genetically engineered pigs in baboons: a comparison of two immunosuppressive regimens. Transplantation. 2019;103(10):2090-2104. Díaz Varela I, Sánchez Mozo P, Centeno Cortés A, et al. Cross-reactivity between swine leukocyte antigen and human anti-HLA-specific antibodies in sensitized patients awaiting renal transplantation. J Am Soc Nephrol. 2003;14(10):2677-2683. Taylor CJ, Tang KG, Smith SI, White DJ, Davies HF. HLA-specific antibodies in highly sensitized patients can cause a positive crossmatch against pig lymphocytes. Transplantation. 1998;65(12):1634-1641. Martens GR, Reyes LM, Li P, et al. Humoral reactivity of renal transplant-waitlisted patients to cells from GGTA1/CMAH/B4GalNT2, and SLA class I knockout pigs. Transplantation. 2017;101(4):e86-e92. Ladowski JM, Reyes LM, Martens GR, et al. Swine leukocyte antigen class II is a xenoantigen. Transplantation. 2018;102(2):249-254. Lunney JK, Ho CS, Wysocki M, Smith DM. Molecular genetics of the swine major histocompatibility complex, the SLA complex. Dev Comp Immunol. 2009;33(3):362-374. Smith DM, Lunney JK, Martens GW, et al. Nomenclature for factors of the SLA class-I system, 2004. Tissue Antigens. 2005;65(2):136-149. Smith DM, Lunney JK, Ho CS, et al. Nomenclature for factors of the swine leukocyte antigen class II system, 2005. Tissue Antigens. 2005;66(6):623-639. Kaulitz D, Mihica D, Dorna J, et al. Development of sensitive methods for detection of porcine endogenous retrovirus-C (PERV-C) in the genome of pigs. J Virol Methods. 2011;175(1):60-65. Kono K, Kataoka K, Yuan Y, Yusa K, Uchida K, Sato Y. A highly sensitive method for the detection of recombinant PERV-A/C env RNA using next generation sequencing technologies. Sci Rep. 2020;10(1):21935. Wynyard S, Nathu D, Garkavenko O, Denner J, Elliott R. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. Xenotransplantation. 2014;21(4):309-323. Matsumoto S, Wynyard S, Giovannangelo M, et al. Long-term follow-up for the microbiological safety of clinical microencapsulated neonatal porcine islet transplantation. Xenotransplantation. 2020;27(6):e12631. Denner J. Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals? Retrovirology. 2018;15(1):28. 10.1186/s12977-018-0411-8. Poppelaars F, Seelen MA. Complement-mediated inflammation and injury in brain dead organ donors. Mol Immunol. 2017;84:77-83. Shimizu A, Yamada K, Robson SC, Sachs DH, Colvin RB. Pathologic characteristics of transplanted kidney xenografts. J Am Soc Nephrol. 2012;23:225-235. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243. Locke JE, Magro CM, Singer AL, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant. 2009;9:231-235. Orandi BJ, Zachary AA, Dagher NN, et al. Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation. 2014;98:857-863. Adams AB, Lovasik BP, Faber DA, et al. Anti-C5 antibody tesidolumab reduces early antibody-mediated rejection and prolongs survival in renal xenotransplantation. Ann Surg. 2021;274:473-480. Kraebber K, Gray E. Addressing regulatory requirements for the organ-source pig-A pragmatic approach to facility design and pathogen prevention. In: Cooper DKC, Byrne G, eds. Clinical Xenotransplantation. Springer International Publishing; 2020. |
| فهرسة مساهمة: | Keywords: clinical research/practice; genetics; kidney transplantation/nephrology; translational research/science; xenoantigen; xenotransplantation |
| تواريخ الأحداث: | Date Created: 20220120 Date Completed: 20220405 Latest Revision: 20230124 |
| رمز التحديث: | 20230126 |
| DOI: | 10.1111/ajt.16930 |
| PMID: | 35049121 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1600-6143 |
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| DOI: | 10.1111/ajt.16930 |