Volume 15 Issue 2
Mar.  2024
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Sun Shengkun, Yang Shujun, Wei Hao, et al. Application of xenotransplantation in clinical practice[J]. ORGAN TRANSPLANTATION, 2024, 15(2): 200-206. doi: 10.3969/j.issn.1674-7445.2023234
Citation: Sun Shengkun, Yang Shujun, Wei Hao, et al. Application of xenotransplantation in clinical practice[J]. ORGAN TRANSPLANTATION, 2024, 15(2): 200-206. doi: 10.3969/j.issn.1674-7445.2023234
shu

Application of xenotransplantation in clinical practice

doi: 10.3969/j.issn.1674-7445.2023234
  • 11.

    Department of Urology, the Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100000, China

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    Abstract
  • Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.

     

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    • References(41)
  • [1]
    许艺红, 肖义军. 猪作为人类器官移植供体的研究进展[J]. 生物学通报, 2022, 57(11): 1-4. DOI: 10.3969/j.issn.0006-3193.2022.11.001.

    XU YH, XIAO YJ. Research progress on pigs as human organ transplant donors[J]. Bull Biol, 2022, 57(11): 1-4. DOI: 10.3969/j.issn.0006-3193.2022.11.001.
    [2]
    窦科峰, 张玄. 临床异种器官移植十大问题的思考[J]. 器官移植, 2022, 13(4): 411-416. DOI: 10.3969/j.issn.1674-7445.2022.04.001.

    DOU KF, ZHANG X. Reflection on 10 problems of clinical xenotransplantation[J]. Organ Transplant, 2022, 13(4): 411-416. DOI: 10.3969/j.issn.1674-7445.2022.04.001.
    [3]
    Um medicine faculty-scientists and clinicians perform second historic transplant of pig heart into patient with end-stage cardiovascular disease[EB/OL]. [2023-11-01].https://www.umms.org/ummc/news/2023/um-medicine-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient.
    [4]
    In memoriam: xenotransplant patient lawrence faucette[EB/OL]. [2023-11-01]. https://www.umms.org/ummc/news/2023/announcing-the-passing-of-lawrence-faucette.
    [5]
    Two-month study of pig kidney xenotransplantation gives new hope to the future of the organ supply[EB/OL]. [2023-11-01]. https://nyulangone.org/news/two-month-study-pig-kidney-xenotransplantation-gives-new-hope-future-organ-supply.
    [6]
    MOAZAMI N, STERN JM, KHALIL K, et al. Pig-to-human heart xenotransplantation in two recently deceased human recipients[J]. Nat Med, 2023, 29(8): 1989-1997. DOI: 10.1038/s41591-023-02471-9.
    [7]
    Porcine kidney xenotransplantation in patients with end-stage kidney disease[EB/OL]. [2023-11-01]. https://clinicaltrials.gov/study/NCT05340426?term=Porcine%20Kidney%20Xenotransplantation%20in%20Patients%20With%20End-Stage%20Kidney%20Disease&rank=1.
    [8]
    HAWTHORNE WJ. World first pig-to-human cardiac xenotransplantation[J]. Xenotransplantation, 2022, 29(1): e12733. DOI: 10.1111/xen.12733.
    [9]
    MOHIUDDIN MM, SINGH AK, SCOBIE L, et al. Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report[J]. Lancet, 2023, 402(10399): 397-410. DOI: 10.1016/S0140-6736(23)00775-4.
    [10]
    GRIFFITH BP, GOERLICH CE, SINGH AK, et al. Genetically modified porcine-to-human cardiac xenotransplantation[J]. N Engl J Med, 2022, 387(1): 35-44. DOI: 10.1056/NEJMoa2201422.
    [11]
    PORRETT PM, ORANDI BJ, KUMAR V, et al. First clinical-grade porcine kidney xenotransplant using a human decedent model[J]. Am J Transplant, 2022, 22(4): 1037-1053. DOI: 10.1111/ajt.16930.
    [12]
    MONTGOMERY RA, STERN JM, LONZE BE, et al. Results of two cases of pig-to-human kidney xenotransplantation[J]. N Engl J Med, 2022, 386(20): 1889-1898. DOI: 10.1056/NEJMoa2120238.
    [13]
    LOUPY A, GOUTAUDIER V, GIARRAPUTO A, et al. Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study[J]. Lancet, 2023, 402(10408): 1158-1169. DOI: 10.1016/S0140-6736(23)01349-1.
    [14]
    GAO M, ZHANG J, WANG R, et al. Pig-to-human xenotransplantation: moving toward organ customization[J]. Precis Clin Med, 2023, 6(2): pbad013. DOI: 10.1093/pcmedi/pbad013.
    [15]
    SINGH AK, CHAN JL, SEAVEY CN, et al. CD4+CD25HiFoxP3+ regulatory T cells in long-term cardiac xenotransplantation[J]. Xenotransplantation, 2018, 25(2): e12379. DOI: 10.1111/xen.12379.
    [16]
    ANAND RP, LAYER JV, HEJA D, et al. Design and testing of a humanized porcine donor for xenotransplantation[J]. Nature, 2023, 622(7982): 393-401. DOI: 10.1038/s41586-023-06594-4.
    [17]
    DENNER J, LÄNGIN M, REICHART B, et al. Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival[J]. Sci Rep, 2020, 10(1): 17531. DOI: 10.1038/s41598-020-73150-9.
    [18]
    NIU D, WEI HJ, LIN L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9[J]. Science, 2017, 357(6357): 1303-1307. DOI: 10.1126/science.aan4187.
    [19]
    LÄNGIN M, MAYR T, REICHART B, et al. Consistent success in life-supporting porcine cardiac xenotransplantation[J]. Nature, 2018, 564(7736): 430-433. DOI: 10.1038/s41586-018-0765-z.
    [20]
    BIKHET M, IWASE H, YAMAMOTO T, et al. What therapeutic regimen will be optimal for initial clinical trials of pig organ transplantation?[J]. Transplantation, 2021, 105(6): 1143-1155. DOI: 10.1097/TP.0000000000003622.
    [21]
    HANSEN-ESTRUCH C, COOPER DKC, JUDD E. Physiological aspects of pig kidney xenotransplantation and implications for management following transplantation[J]. Xenotransplantation, 2022, 29(3): e12743. DOI: 10.1111/xen.12743.
    [22]
    HINRICHS A, RIEDEL EO, KLYMIUK N, et al. Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies[J]. Xenotransplantation, 2021, 28(2): e12664. DOI: 10.1111/xen.12664.
    [23]
    ADAMS A, CENDALES LC, COOPER DKC, et al. American Society of Transplant Surgeons-American Society of Transplantation report of FDA meeting on regulatory expectations for xenotransplantation products[J]. Am J Transplant, 2023, 23(9): 1290-1299. DOI: 10.1016/j.ajt.2023.05.010.
    [24]
    IWASE H, HARA H, EZZELARAB M, et al. Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts[J]. Xenotransplantation, 2017, 24(2): e12293. DOI: 10.1111/xen.12293.
    [25]
    COOPER DKC, HARA H, IWASE H, et al. Pig kidney xenotransplantation: progress toward clinical trials[J]. Clin Transplant, 2021, 35(1): e14139. DOI: 10.1111/ctr.14139.
    [26]
    IWASE H, YAMAMOTO T, COOPER DKC. Episodes of hypovolemia/dehydration in baboons with pig kidney transplants: a new syndrome of clinical importance?[J]. Xenotransplantation, 2019, 26(2): e12472. DOI: 10.1111/xen.12472.
    [27]
    ADAMS AB, KIM SC, MARTENS GR, et al. Xenoantigen deletion and chemical immunosuppression can prolong renal xenograft survival[J]. Ann Surg, 2018, 268(4): 564-573. DOI: 10.1097/SLA.0000000000002977.
    [28]
    GOLDSTONE AB, BACHA EA, SYKES M. On cardiac xenotransplantation and the role of xenogeneic tolerance[J]. J Thorac Cardiovasc Surg, 2023, 166(3): 968-972. DOI: 10.1016/j.jtcvs.2022.11.036.
    [29]
    MOHIUDDIN MM, GOERLICH CE, SINGH AK, et al. Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months[J]. Xenotransplantation, 2022, 29(3): e12744. DOI: 10.1111/xen.12744.
    [30]
    YAMAMOTO T, LADOWSKI JM, BIKHET M, et al. Efficacy of ATG and rituximab in capuchin monkeys (a new world monkey)-an in vitro study relevant to xenotransplantation[J]. Xenotransplantation, 2020, 27(6): e12627. DOI: 10.1111/xen.12627.
    [31]
    YAMAMOTO T, HARA H, FOOTE J, et al. Life-supporting kidney xenotransplantation from genetically engineered pigs in baboons: a comparison of two immunosuppressive regimens[J]. Transplantation, 2019, 103(10): 2090-2104. DOI: 10.1097/TP.000000000000 2796.
    [32]
    BÜHLER L, AWWAD M, BASKER M, et al. High-dose porcine hematopoietic cell transplantation combined with CD40 ligand blockade in baboons prevents an induced anti-pig humoral response[J]. Transplantation, 2000, 69(11): 2296-2304. DOI: 10.1097/00007890-200006150-00013.
    [33]
    TUCK N. Animals in moral limbo: how literary pigs may help lab-generated ones[J]. Animals (Basel), 2020, 10(4): 629. DOI: 10.3390/ani10040629.
    [34]
    EL MASRI J, AFYOUNI A, GHAZI M, et al. Current state of clinical trials on xenograft[J]. Xenotransplantation, 2023, 30(3): e12801. DOI: 10.1111/xen.12801.
    [35]
    For physicians: how to request single patient expanded access (“compassionate use”) [EB/OL]. [2023-11-01]https://www.fda.gov/drugs/investigational-new-drug-ind-application/physicians-how-request-single-patient-expanded-access-compassionate-use.
    [36]
    SADE RM, MUKHERJEE R. Ethical issues in xenotransplantation: the first pig-to-human heart transplant[J]. Ann Thorac Surg, 2022, 113(3): 712-714. DOI: 10.1016/j.athoracsur.2022.01.006.
    [37]
    SPILLMAN MA, SADE RM. Clinical trials of xenotransplantation: waiver of the right to withdraw from a clinical trial should be required[J]. J Law Med Ethics, 2007, 35(2): 265-272. DOI: 10.1111/j.1748-720X.2007.00135.x.
    [38]
    杨树军,卫浩,彭江,等. 中国公众对异种肾移植接受度的预测模型构建及验证 [J]. 器官移植, 2024,15(1):102-111. DOI: 10.3969/j.issn.1674-7445.2023164.

    YANG SJ, WEI H, PENG J, et al. Construction and validation of a prediction model for public acceptance of kidney xenotransplantation in China[J]. Organ Transplant, 2024,15(1):102-111. DOI: 10.3969/j.issn.1674-7445.2023164.
    [39]
    DAS S, KOYANO-NAKAGAWA N, GAFNI O, et al. Generation of human endothelium in pig embryos deficient in ETV2[J]. Nat Biotechnol, 2020, 38(3): 297-302. DOI: 10.1038/s41587-019-0373-y.
    [40]
    WANG J, XIE W, LI N, et al. Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation[J]. Cell Stem Cell, 2023, 30(9): 1235-1245. DOI: 10.1016/j.stem.2023.08.003.
    [41]
    COOPER DKC, HARA H. "You cannot stay in the laboratory forever"*: taking pig kidney xenotransplantation from the laboratory to the clinic[J]. EBioMedicine, 2021, 71: 103562. DOI: 10.1016/j.ebiom.2021.103562.
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