New advances in xenotransplantation: from bench to bedside_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Danni , ZHAO Yanshuang , WANG Yi , PAN Dengke ,  DENG Shaoping

Institute of Organ Transplantation, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610072, P. R. China;

Corresponding author：

DENG Shaoping, Email: sdeng10@163.com

Keywords：

heart transplant; xenotransplantation; gene-edited pigs; immune rejection

DOI：

10.7507/1007-9424.202204023

Video：

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Abstract Full text Figures/Tables Video References Cited by

On January 7, 2022, the University of Maryland Medical Center reported that the world’s first gene-edited pig heart was successfully transplanted into a 57-year-old man with end-stage heart disease, causing a global attention. The first gene-edited pig heart transplanted into a human successfully survived for 59 d without showing early signs of rejection, creating a history of xenotransplantation and marking a key step forward the clinical development of xenotransplantation. This article focuses on the role of gene editing in alleviating immune rejection, summarizes the case of xenotransplantation at the Maryland Medical Center, and outlines the current status of xenotransplantation and the unresolved issues of xenotransplantation. It is expected that xenotransplantation can successfully enter the clinic in the near future.

Citation： LI Danni, ZHAO Yanshuang, WANG Yi, PAN Dengke, DENG Shaoping. New advances in xenotransplantation: from bench to bedside. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(6): 705-710. doi: 10.7507/1007-9424.202204023 Copy

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14.	Gollackner B, Goh SK, Qawi I, et al. Acute vascular rejection of xenografts: roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity. Transplantation, 2004, 77(11): 1735-1741.
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1. Yong Guang Yang, Megan Sykes. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol, 2007, 7(7): 519-531.
2. Dobric M. Life-saving organ donation statistics and facts for 2022.https://medalerthelp. org/blog/ organ-donation-statistics.
3. Shah AM, Han JJ. First successful porcine to human heart transplantation performed in the United States. Artif Organs, 2022, 46(4): 543-545.
4. Phelps CJ, Koike C, Vaught TD, et al. Production of alpha 1, 3-galactosyltransferase-deficient pigs. Science, 2003, 299(5605): 411-414.
5. 于佳庆, 方铭慧, 安培培, 等. 猪肾脏异种移植的研究进展. 吉林大学学报(医学版), 2021, 47(3): 788-795.
6. Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest, 2003, 111(8): 1122-1124.
7. Mohiuddin MM, Singh AK, Corcoran PC, et al. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO. hCD46. hTBM pig-to-primate cardiac xenograft. Nat Commun, 2016, 7: 11138. doi: 10.1038/ncomms11138.
8. 杨佩军, 李霄, 窦科峰. GTKO 猪 α-1, 3- 半乳糖苷转移酶检测方法的进展. 实用器官移植电子杂志, 2018, 6(5): 409-411.
9. Lai L, Kolber-Simonds D, Park KW, et al. Production of alpha-1, 3-galacto syltransferase knockout pigs by nuclear transfer cloning. Science, 2002, 295(5557): 1089-1092.
10. Diswall M, Angström J, Karlsson H, et al. Structural characterization of α1, 3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies. Xenotransplatation, 2010, 17(1): 48-60.
11. Ménoret S, Plat M, Blancho G, et al. Characterization of human CD55 and CD59 transgenic pigs and kidney xenotransplantation in the pig-to-baboon combination. Transplantation, 2004, 77(9): 1468-1471.
12. Mohiuddin MM, Corcoran PC, Singh AK, et al. B-cell depletion extends the survival of GTKO. hCD46Tg pig heart xenografts in baboons for up to 8 months. Am J Transplant, 2012, 12(3): 763-771.
13. 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(1): 29-31.
14. Gollackner B, Goh SK, Qawi I, et al. Acute vascular rejection of xenografts: roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity. Transplantation, 2004, 77(11): 1735-1741.
15. Lin CC, Cooper DK, Dorling A. Coagulation dysregulation as a barrier to xenotransplantation in the primate. Transpl Immunol, 2009, 21(2): 75-80.
16. Takeuchi K, Ariyoshi Y, Shimizu A, et al. Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation. Xenotransplantation, 2021, 28(6): e12708. doi: 10.1111/xen.12708.
17. NYU Langone Health. Progress in xenotransplantation opens door to new supply of critically needed organs. https://nyulangone.org/news/progress-xenotransplantation-opens-door-new-supply-critically-needed-organs.
18. Authored by scitechdaily. com and submitted by a_Ninja_b0y. Successful xenotransplantation surgery: genetically engineered pig kidney transplanted to human body.https://dailypopulous. com/2021-12-16-evening/successful-xenotransplantation-surgery-genetically-engineered-pig-kidney-transplanted-to.html.
19. Porrett PM, Orandi BJ, Kumar V, et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant, 2022, 22(4): 1037-1053.
20. 王维, 窦科峰, 王贵强, 等. 异种胰岛移植临床研究专家共识 (2019专家建议版). 器官移植, 2019, 10(6): 672-677.
21. Feng H, Li T, Du JX, et al. Both natural and induced anti-Sda antibodies play important roles in GTKO pig-to-rhesus monkey xenotransplantation. Frontiers in Immunology, 2022, 13: 849711. doi: 10.3389/fimmu.2022.849711.
22. Pan D, Liu T, Lei T, et al. Progress in multiple genetically modified minipigs for xenotransplantation in China. Xenotransplantation, 2019, 26(1): e12492. doi: 10.1111/xen.12492.
23. 唐红梅, 李欣, 周佳, 等. GGTA1基因敲除猪胰岛细胞移植到Ⅰ型糖尿病猕猴3例报道. 2021, 28(5): 561-565.
24. Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science, 2017, 357(6357): 1238-1303.
25. Sykes M, Sandrin M, D'Apice A, et al. Guidelines for xenotransplantation. N Engl J Med, 2003, 25,349(13): 1294-1295.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

New advances in xenotransplantation: from bench to bedside

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