Volume 9 Issue 3
May  2018
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2018  >  9(3): 174-180
Wu Enhao, Li Xiao, Tao Kaishan. Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002
Citation: Wu Enhao, Li Xiao, Tao Kaishan. Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002
shu

Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation

doi: 10.3969/j.issn.1674-7445.2018.03.002

  • Department of Hepatobilliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, 710032, China

More Information
  • Corresponding author: Tao Kaishan, Email: taokaishan0686@163.com
  • Received Date: 2018-01-15
    Available Online: 2021-01-19
  • Publish Date: 2018-05-15
    Abstract
  •   Objective  To investigate the mechanism underlying the activation of tissue factor (TF) that leads to coagulation dysfunction in the recipients after liver xenotransplantation.  Methods  Auxiliary heterotopic liver xenotransplantation was performed in 3 minipigs with α-1, 3-galactosyltransferase gene-knockout (GTKO) as the donors and Tibetan macaque (Macaca thibetana) as the recipients. Postoperative coagulation function changes in the recipients were observed. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were adopted to quantitatively measure the expression levels of monkey and minipig TF messenger RNA (mRNA) and protein in the liver tissues of the primary and transplant livers at different time points before and after transplantation. The recalcification time of peripheral blood mononuclear cell (PBMC) was recorded in the normal control monkeys and the recipient monkeys before and 2 h after liver transplantation to evaluate the coagulation status in the recipients.  Results  All three recipients presented with different degrees of coagulation dysfunction after surgery, manifested as a decrease in fibrinogen level and a reduction in platelet count. The monkey TF protein was positively expressed in the primary livers after surgery, whereas negatively expressed in transplant livers before and after liver transplantation. The minipig TF protein was negatively expressed in both primary livers and transplant livers. At postoperative 2 h, monkey TF mRNA was up-regulated by (2.10±0.24) times in the primary liver compared with the preoperative level, whereas the minipig TF mRNA was up-regulated by (1.42±0.15) times compared with preoperative level. There was statistical significance between the primary livers and transplant livers ( P=0.014). Compared with PBMC in the normal control monkeys and recipient monkeys before liver transplantation, the recalcification time of the PBMC in the recipient monkeys was significantly shortened at postoperative 2 h (both P < 0.001).  Conclusions  At the presence of coagulation dysfunction after liver xenotransplantation, the level of TF activation in the primary livers is significantly higher than that in the transplant livers. The TF activation in the primary livers is the main cause of coagulation dysfunction after liver xenotransplantation.

     

    • FullText(HTML)
  • loading
    • References(15)
  • [1]
    夏强.突破肝移植的瓶颈阶段[J].肝胆外科杂志, 2010, 18(3): 164-166. DOI: 10.3969/j.issn.1006-4761.2010.03.002.

    XIA Q. Breaking through the bottleneck stage of liver transplantation[J]. J Hepatobiliary Surg, 2010, 18(3): 164- 166. DOI: 10.3969/j.issn.1006-4761.2010.03.002.
    [2]
    MUELLER NJ, EZZELARAB M, BUHLER L, et al. Monitoring of porcine and baboon cytomegalovirus infection in xenotransplantation[J]. Xenotransplantation, 2 0 0 9, 1 6 (6) : 5 3 5 - 5 3 6. D O I : 1 0. 1111 / j. 1 3 9 9 - 3089.2009.00536.x.
    [3]
    陶开山, 李霄, 窦科峰.异种肝移植的历史与发展[J].器官移植, 2017, 8(2): 85-88. DOI: 10.3969/j.issn.1674-7445.2017.02.001.

    TAO KS, LI X, DOU KF. History and development of liver xenotransplantation[J]. Organ Transplant, 2017, 8(2): 85- 88. DOI: 10.3969/j.issn.1674-7445.2017.02.001.
    [4]
    EKSER B, EZZELARAB M, HARA H, et al. Clinical xenotransplantation: the next medical revolution?[J]. Lancet, 2012, 379(9816): 672-683. DOI: 10.1016/S0140- 6736(11)61091-X.
    [5]
    EKSER B, COOPER DK. Overcoming the barriers to xenotransplantation: prospects for the future[J]. Expert Rev Clin Immunol, 2010, 6(2): 219-230. doi: 10.1586/eci.09.81
    [6]
    PULLEN LC. Xenotransplantation: time to get excited?[J]. Am J Transplant, 2017, 17(12): 2995-2996. DOI: 10.1111/ajt.14553.
    [7]
    EKSER B, LI P, COOPER DKC. Xenotransplantation: past, present, and future[J]. Curr Opin Organ Transplant, 2017, 22(6): 513-521. DOI: 10.1097/MOT.0000000000000463.
    [8]
    SAHARA H, WATANABE H, POMPOSELLI T, et al. Lung xenotransplantation[J]. Curr Opin Organ Transplant, 2017, 22(6):541-548. DOI: 10.1097/MOT.0000000000000465.
    [9]
    LIN CC, CHEN D, MCVEY JH, et al. Expression of tissue factor and initiation of clotting by human platelets and monocytes after incubation with porcine endothelial cells[J]. Transplantation, 2008, 86(5): 702-709. DOI: 10.1097/TP.0b013e31818410a3.
    [10]
    NAGAYASU T, SAADI S, HOLZKNECHT RA, et al. Expression of tissue factor mRNA in cardiac xenografts:clues to the pathogenesis of acute vascular rejection[J]. Transplantation, 2000, 69(4):475-482. doi: 10.1097/00007890-200002270-00003
    [11]
    EKSER B, LIN CC, LONG C, et al. Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation[J]. Transpl Int, 2012, 25(8):882- 896. DOI: 10.1111/j.1432-2277.2012.01506.x.
    [12]
    LIN CC, EZZELARAB M, HARA H, et al. Atorvastatin or transgenic expression of TFPI inhibits coagulation initiated by anti-nonGal IgG binding to porcine aortic endothelial cells[J]. J Thromb Haemost, 2010, 8(9): 2001-2010. DOI: 10.1111/j.1538-7836.2010.03950.x.
    [13]
    KIM K, SCHUETZ C, ELIAS N, et al. Up to 9-day survival and control of thrombocytopenia following alpha1, 3-galactosyl transferase knockout swine liver xenotransplantation in baboons[J]. Xenotransplantation, 2012, 19(4):256-264. DOI: 10.1111/j.1399-3089.2012. 00717.x.
    [14]
    LIN CC, EZZELARAB M, SHAPIRO R, et al. Recipient tissue factor expression is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation[J]. Am J Transplant, 2010, 10(7):1556- 1568. DOI: 10.1111/j.1600-6143.2010.03147.x.
    [15]
    BROZE GJ JR, GIRARD TJ. Tissue factor pathway inhibitor: structure-function[J]. Front Biosci (Landmark Ed), 2012, 17:262-280. doi: 10.2741/3926
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (65) PDF downloads(5) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return