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中华损伤与修复杂志(电子版) ›› 2022, Vol. 17 ›› Issue (02) : 163 -166. doi: 10.3877/cma.j.issn.1673-9450.2022.02.014

综述

基因工程猪皮的研究进展
李峰1,(), 黎君友2   
  1. 1. 100048 北京,解放军总医院第四医学中心烧伤整形医学部
    2. 100048 北京,解放军总医院创伤研究中心
  • 收稿日期:2022-01-07 出版日期:2022-04-01
  • 通信作者: 李峰
  • 基金资助:
    科技部国家重点研发计划(2017YFD0501606)

Research progress on skin from genetically engineered pigs

Feng Li1,(), Junyou Li2   

  1. 1. Department of Burns and Plastic Surgery, Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100048, China
    2. Trauma Research Center, Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100048, China
  • Received:2022-01-07 Published:2022-04-01
  • Corresponding author: Feng Li
引用本文:

李峰, 黎君友. 基因工程猪皮的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2022, 17(02): 163-166.

Feng Li, Junyou Li. Research progress on skin from genetically engineered pigs[J/OL]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2022, 17(02): 163-166.

采用异体皮(或异种皮)覆盖烧伤创面是大面积烧伤治疗的关键措施之一。在异体皮不易获得的情况下,采用异种皮特别是猪皮临时覆盖创面也可以起到一定的治疗作用。但由于种属间的免疫屏障,普通猪皮在人体创面上覆盖时间短、与创面之间不能建立血管网络,其治疗作用远逊于异体皮。近年来通过基因工程对供体猪进行基因改造,包括基因敲除与基因转入,可在一定程度上降低人体对移植物的排斥反应,延长异种皮片的存活时间。本文就用于异种移植的基因工程猪皮的相关研究进展进行综述。

The use of allogeneic skin (or xeno-skin) to cover the burn wound is one of the key measure for extensive burn treatment. When allogeneic skin is not easy to obtain, temporary covering of the wound with xenograft of skin, especially pig skin, can also play a certain therapeutic effect. Due to the immune barrier between species, ordinary pig skin covers the human wound for a short time and cannot form vascularization with the wound. In recent years, genetic modification of donor pigs through genetic engineering, including gene knockout and gene transfer, can reduce the rejection of transplants by the human to a certain extent and prolong the survival time of xenografts. This article reviews the research progress of genetically engineered pig skin for xenotransplantation.

[1]
朱兆明,柴家科,贾晓明. 皮肤储存基础与应用[M]. 北京:人民军医出版社,2002: 183.
[2]
青春,史济湘. 烧伤创面覆盖物[J]. 生物医学工程学杂志1995, 12(1): 82-86.
[3]
Heimbach D, Luterman A, Burke J, et al. Artificial dermis for major burns. A multi-center randomized clinical trial[J]. Ann Surg, 1988, 208(3): 313-320.
[4]
Conor Hale. FDA clears first xenotransplantation trial of skin cells derived from genetically engineered[EB/OL]. (2018-12-12)[2021-03-18].

URL    
[5]
Goverman J. Mass General performs first application of genetically modified, live-cell, pig skin to a human wound[EB/OL]. (2019-10-11) [2021-03-18].

URL    
[6]
步宏,王华,魏启欧,等. 中国近交系猪到人异种移植靶抗原研究[J]. 中国修复重建外科杂志2000, 14(2): 115-118.
[7]
Galili U, Mandrell RE, Hamadeh RM, et al. Interaction Between Human Natural Anti-Alpha-Galactosyl Immunoglobulin G and Bacteria of the Human Flora[J]. Infect Immun, 1988, 56(7): 1730-1737.
[8]
Yamamoto T, Iwase H, King TW, et al. Skin xenotransplantation: Historical review and clinical potential[J]. Burns, 2018, 44(7): 1738-1749.
[9]
Lai L, Kolber-Simonds D, Park KW, et al. Production of α-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning[J]. Science, 2002, 295(5557): 1089-1092.
[10]
Weiner J, Yamada K, Ishikawa Y, et al. Prolonged survival of GalT-KO swine skin on baboons[J]. Xenotransplantation, 2010, 17(2): 147-152.
[11]
Leto Barone AA, Mastroianni M, Farkash EA, et al. Genetically modified porcine split-thickness skin grafts as an alternative to allograft for provision of temporary wound coverage: preliminary characterization[J]. Burns, 2015, 41(3): 565-574.
[12]
Leonard DA, Mallard C, Albritton A, et al. Skin grafts from genetically modified a-1,3-galactosyltransferase knockout miniature swine: A functional equivalent to allografts[J]. Burns, 2017, 43(8): 1717-1724.
[13]
Holzer PW, Chang E, Wicks J, et al. Immunological response in cynomolgus macaques to porcine α-1,3 galactosyltransferase knockout viable skin xenotransplants—A pre-clinical study[J]. Xenotransplantation, 2020, 27(6): e12632.
[14]
Azimzadeh AM, Kelishadi SS, Ezzelarab MB, et al. Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein[J]. Xenotransplantation, 2015, 22(4): 310-316.
[15]
Ezzelarab MB, Ayares D, Cooper DK. Transgenic expression of human CD46: does it reduce the primate T-cell response to pig endothelial cells?[J]. Xenotransplantation, 2015, 22(6): 487-489.
[16]
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[J]. Am J Transplant, 2012, 12(3): 763-771.
[17]
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[J]. Nat Commun, 2016, 7: 11138.
[18]
Singh AK, Chan JL, DiChiacchio L, et al. Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs[J]. Xenotransplantation, 2019, 26(2): e12465.
[19]
Ezzelarab M, Cooper DK. Reducing Gal expression on the pig organ - a retrospective review[J]. Xenotransplantation, 2005, 12(4): 278-285.
[20]
Fujita T, Miyagawa S, Ezoe K, et al. Skin graft of double transgenic pigs of N-acetylglucosaminyltransferase III (GnT-III) and DAF (CD55) genes survived in cynomolgus monkey for 31 days[J]. Transpl Immunol, 2004, 13(4): 259-264.
[21]
Gao B, Long C, Lee W, et al. Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans[J]. PLoS One, 2017, 12(7): e0180768.
[22]
Tector AJ, Mosser M, Tector M, et al. The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation[J]. Front Immunol, 2020, 11: 622.
[23]
Scobie L, Padler-Karavani V, Le Bas-Bernardet S, et al. Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts[J]. J Immunol, 2013, 191: 2907-2915.
[24]
Cooper DK. Modifying the sugar icing on the transplantation cake[J]. Glycobiology, 2016, 26(6): 571-581.
[25]
Wang RG, Ruan M, Zhang RJ, et al. Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs[J]. J Biomed Res, 2018, 33(4): 235-243.
[26]
Cooper DKC, Ezzelarab M, Iwase H, et al. Perspectives on the Optimal Genetically Engineered Pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation[J]. Transplantation, 2018, 102(12): 1974-1982.
[27]
Yamamoto T, Iwase H, Patel D, et al. Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout)[J]. Sci Rep, 2020, 10(1): 9771.
[28]
Ge L, Xiong F, Zhang W, et al. In vitro Ad5F35-mediated CTLA4-Ig gene transfer prolongs pig skin xenotransplant survival[J]. Transplant Proc, 2010, 42(9): 3763-3766.
[29]
马兵,易绍萱,刘月明,等. CTLA4Ig基因转染猪皮治疗中小面积浅Ⅱ度烧伤创面的随机对照试验[J/CD]. 中华损伤与修复杂志(电子版), 2008, 3(3): 305-309.
[30]
刘漪沦,马兵,刘月明,等. 基因转染猪皮在大面积深度烧伤患者微粒皮移植中的临床应用[J]. 四川医学2009, 30(5): 623-624.
[31]
Wang Y, Yang HQ, Jiang W, et al. Transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) by porcine skin for xenogeneic skin grafting[J]. Transgenic Res, 2015, 24(2): 199-211.
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