留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

六基因修饰巴马小型猪活体供肾切取研究报告

许勇, 宋翔宇, 王恒恩, 等. 六基因修饰巴马小型猪活体供肾切取研究报告[J]. 器官移植, 2024, 15(2): 229-235. doi: 10.3969/j.issn.1674-7445.2023215
引用本文: 许勇, 宋翔宇, 王恒恩, 等. 六基因修饰巴马小型猪活体供肾切取研究报告[J]. 器官移植, 2024, 15(2): 229-235. doi: 10.3969/j.issn.1674-7445.2023215
Xu Yong, Song Xiangyu, Wang Heng’en, et al. Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified[J]. ORGAN TRANSPLANTATION, 2024, 15(2): 229-235. doi: 10.3969/j.issn.1674-7445.2023215
Citation: Xu Yong, Song Xiangyu, Wang Heng’en, et al. Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified[J]. ORGAN TRANSPLANTATION, 2024, 15(2): 229-235. doi: 10.3969/j.issn.1674-7445.2023215

六基因修饰巴马小型猪活体供肾切取研究报告

doi: 10.3969/j.issn.1674-7445.2023215
基金项目: 国家重点研发计划(2019YFA0110704)
详细信息
    作者简介:
    通讯作者:

    孙圣坤(ORCID 0000-0002-6463-6425),博士,主任医师,副教授,研究方向为异种器官移植和尿路上皮肿瘤,Email:sunshengkun@301hospital.com.cn

  • 中图分类号: R617, R692

Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified

More Information
  • 摘要:   目的  总结基因修饰猪活体供肾切取的经验及其实践价值。  方法  采用活体供肾切取技术,切取六基因修饰猪左侧肾脏。首先阻断输尿管,游离下腔静脉及腹主动脉后,切取过程中依次完成输尿管、肾静脉、肾动脉的显露、游离。在腹主动脉、下腔静脉上阻断钳,离断肾动脉、静脉后立即用4 ℃肾保存液进行灌注,保存在冰生理盐水中准备移植。同时完成供体腹主动脉、下腔静脉缺口的缝合。记录手术时间,出血量,热缺血和冷缺血时间,并发症发生情况以及供、受体存活情况。  结果  成功切取基因修饰猪左肾,取肾术中出血5 mL,热缺血时间45 s,冷缺血时间2.5 h。供、受体均未输血,植入受体内的肾脏恢复泌尿功能。切取左肾后供体健康存活8个月余。  结论  基因修饰猪活体供肾切取技术安全可靠,游离肾脏过程中同时处理分支血管,减少了修肾过程,缩短了冷缺血时间,活体供肾切取有助于后续供体存活并进行其他科学研究。

     

  • FIG. 2993.  FIG. 2993.

    FIG. 2993..  FIG. 2993.

    图  1  活体供肾切取示意图

    注:A图示预计切开的血管位置;B图示在血管根部离断肾静脉及动脉;C图示缝合下腔静脉、腹主动脉缺损。

    Figure  1.  Schematic diagram of living donor nephrectomy

    图  2  活体供肾切取过程

    注:A图示夹闭输尿管末端;B图示游离左肾静脉;C图示游离左肾动脉;D图示供肾动脉离断;E图示供肾静脉离断;F图示供肾灌注及修整。

    Figure  2.  The procedure of living donor nephrectomy

    图  3  缝合腹主动脉及下腔静脉缺口

    Figure  3.  Suturing the notch of abdominal aorta and inferior vena cava

    表  1  供体猪血常规检测

    Table  1.   Routine blood test of the donor pig

    时间 红细胞
    (×1012/L)
    白细胞
    (×109/L)
    淋巴细胞
    (×109/L)
    血红蛋白
    (g/L)
    红细胞比容
    平均红细胞
    体积(/fL)
    平均红细胞血红
    蛋白量(/pg)
    平均红细胞血红
    蛋白浓度(g/L)
    术前 6.02 11.21 7.56 120 0.34 54.5 18.3 344
    术后8个月 5.83 11.79 6.87 116 0.31 59.1 20.6 342
    正常值 5.50~9.00 10.20~30.00 4.80~16.20 100~160 0.33~0.52 51.0~73.0 14.0~22.0 300~360
    下载: 导出CSV
  • [1] SYKES M, SACHS DH. Transplanting organs from pigs to humans[J]. Sci Immunol, 2019, 4(41): eaau6298. DOI: 10.1126/sciimmunol.aau6298.
    [2] YAMADA K, ARIYOSHI Y, POMPOSELLI T, et al. Co-transplantation of vascularized thymic graft with kidney in pig-to-nonhuman primates for the induction of tolerance across xenogeneic barriers[J]. Methods Mol Biol, 2020, 2110: 151-171. DOI: 10.1007/978-1-0716-0255-3_11.
    [3] 赵恒, 徐凯祥, 范柠粼, 等. 基因编辑异种移植供体猪的构建及现状[J/CD]. 实用器官移植电子杂志, 2018, 6(5): 412-418. DOI: 10.3969/j.issn.2095-5332.2018.05.018.

    ZHAO H, XU KX, FAN NL, et al. Construction and current status of genetically edited xenograft donor pigs [J/CD]. Pract J Organ Transplant(Electr Vers), 2018, 6(5): 412-418. DOI: 10.3969/j.issn.2095-5332.2018.05.018.
    [4] VERNOOIJ RWM, LAW W, PETERS SAE, et al. The probability of receiving a kidney transplantation in end-stage kidney disease patients who are treated with haemodiafiltration or haemodialysis: a pooled individual participant data from four randomised controlled trials[J]. BMC Nephrol, 2021, 22(1): 70. DOI: 10.1186/s12882-021-02265-6.
    [5] BURGAN CM, SUMMERLIN D, LOCKHART ME. Renal transplantation: pretransplant workup, surgical techniques, and surgical anatomy[J]. Radiol Clin North Am, 2023, 61(5): 797-808. DOI: 10.1016/j.rcl.2023.04.003.
    [6] WANG Y, LEI T, WEI L, et al. Xenotransplantation in China: present status[J]. Xenotransplantation, 2019, 26(1): e12490. DOI: 10.1111/xen.12490.
    [7] COZZI E, SCHNEEBERGER S, BELLINI MI, et al. Organ transplants of the future: planning for innovations including xenotransplantation[J]. Transpl Int, 2021, 34(11): 2006-2018. DOI: 10.1111/tri.14031.
    [8] 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.
    [9] RODGER D, HURST DJ, COOPER DK. Xenotransplantation: a historical-ethical account of viewpoints[J]. Xenotransplantation, 2023, 30(2): e12797. DOI: 10.1111/xen.12797.
    [10] SYKES M, SACHS DH. Progress in xenotransplantation: overcoming immune barriers[J]. Nat Rev Nephrol, 2022, 18(12): 745-761. DOI: 10.1038/s41581-022-00624-6.
    [11] ARABI TZ, SABBAH BN, LERMAN A, et al. Xenotransplantation: current challenges and emerging solutions[J]. Cell Transplant, 2023, 32: 9636897221148771. DOI: 10.1177/09636897221148771.
    [12] 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.
    [13] SINGH AK, CHAN JL, SEAVEY CN, et al. CD4+CD25Hi FoxP3+ regulatory T cells in long-term cardiac xenotransplantation[J]. Xenotransplantation, 2018, 25(2): e12379. DOI: 10.1111/xen.12379.
    [14] HAWTHORNE WJ. World first pig-to-human cardiac xenotransplantation[J]. Xenotransplantation, 2022, 29(1): e12733. DOI: 10.1111/xen.12733.
    [15] 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.
    [16] BALIGA RR. Genetically modified porcine-to-human cardiac xenotransplantation[J]. N Engl J Med, 2022, 387(14): 1337-1338. DOI: 10.1056/NEJMc2210401.
    [17] 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.
    [18] 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.
    [19] 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.
    [20] 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.
    [21] NIH National Library of Medicine. Porcine kidney xenotransplantation in patients with end-stage kidney disease[EB/OL]. [2023-10-01]. https://clinicaltrials.gov/study/NCT05340426.
    [22] LEE K, FARRELL K, UH K. Application of genome-editing systems to enhance available pig resources for agriculture and biomedicine[J]. Reprod Fertil Dev, 2019, 32(2): 40-49. DOI: 10.1071/RD19273.
    [23] PETERSEN B, FRENZEL A, LUCAS-HAHN A, et al. Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic microinjection of CRISPR/Cas9 into zygotes[J]. Xenotransplantation, 2016, 23(5): 338-346. DOI: 10.1111/xen.12258.
    [24] COOPER DKC. What will be the cost of a genetically-engineered pig organ for clinical xenotransplantation?[J]. Xenotransplantation, 2020, 27(5): e12606. DOI: 10.1111/xen.12606.
    [25] 刘圣圳, 董隽, 罗光达, 等. 机器人辅助腹腔镜活体供肾切取术(附2例报告)[J]. 微创泌尿外科杂志, 2015(2): 75-77. DOI: 10.3969/j.issn.2095-5146.2015.02.003.

    LIU SZ, DONG J, LUO GD, et al. Robotic-assisted living donor nephrectomy (two cases of reports)[J]. J Minim Invasive Urol, 2015(2): 75-77. DOI: 10.3969/j.issn.2095-5146.2015.02.003.
    [26] 董隽, 卢锦山, 祖强, 等. 改良手辅助后腹腔镜活体供肾切取术(附视频)[J/CD]. 中华移植杂志(电子版), 2010, 4(3): 219-220. DOI: 10.3877/cma.j.issn.1674-3903.2010.03.010.

    DONG J, LU JS, ZU Q, et al. Modified hand-assisted retrolaparoscopic living donor nephrectomy [J/CD]. Chin J Transplant (Electr Edit), 2010, 4(3): 219-220. DOI: 10.3877/cma.j.issn.1674-3903.2010.03.010.
    [27] OZTURK SA, YUKSEL Y, ERBIS H, et al. Laparoscopic live donor nephrectomy: experience of high-volume center with 2, 477 cases[J]. Urol Int, 2021, 105(1/2): 100-107. DOI: 10.1159/000511377.
    [28] TIONG HY, GOH BYS, CHIONG E, et al. Robotic kidney autotransplantation in a porcine model: a procedure-specific training platform for the simulation of robotic intracorporeal vascular anastomosis[J]. J Robot Surg, 2018, 12(4): 693-698. DOI: 10.1007/s11701-018-0806-5.
    [29] 王西墨. 猪到猕猴异种肾移植的实验研究[D]. 湖北: 华中科技大学, 2001. DOI: 10.7666/d.y392889.
    [30] 郭霜, 李选鹏, 满江位, 等. 手助后腹腔镜和开放活体供肾切取术的临床分析[J]. 微创泌尿外科杂志, 2019, 8(1): 1-6. DOI: 10.19558/j.cnki.10-1020/r.2019.01.001.

    GUO S, LI XP, MAN JW, et al. Clinical analysis of hand-assisted retroperitoneoscopic and open living donor nephrectomy[J]. J Minim Invasive Urol, 2019, 8(1): 1-6. DOI: 10.19558/j.cnki.10-1020/r.2019.01.001.
    [31] 雷永生, 王志伟, 王钢, 等. 后腹腔镜右侧活体供肾切取术单中心经验[J/CD]. 中华移植杂志(电子版), 2020, 14(4): 234-236. DOI: 10.3877/cma.j.issn.1674-3903.2020.04.008.

    LEI YS, WANG ZW, WANG G, et al. Single center experience in retrolaparoscopic right living donor nephrectomy [J/CD] . Chin J Transplant (Electr Edit), 2020, 14(4): 234-236. DOI: 10.3877/cma.j.issn.1674-3903.2020.04.008.
    [32] DAGNÆS-HANSEN J, KRISTENSEN GH, STROOMBERG HV, et al. Surgical approaches and outcomes in living donor nephrectomy: a systematic review and meta-analysis[J]. Eur Urol Focus, 2022, 8(6): 1795-1801. DOI: 10.1016/j.euf.2022.03.021.
    [33] WINDISCH OL, MATTER M, PASCUAL M, et al. Robotic versus hand-assisted laparoscopic living donor nephrectomy: comparison of two minimally invasive techniques in kidney transplantation[J]. J Robot Surg, 2022, 16(6): 1471-1481. DOI: 10.1007/s11701-022-01393-x.
    [34] NEWMAN ME, MUSK GC, HE B. Establishment of laparoscopic live donor nephrectomy in a porcine model: techniques and outcomes in 44 pigs[J]. J Surg Res, 2018, 222: 132-138. DOI: 10.1016/j.jss.2017.09.042.
    [35] GKEKA K, TSATURYAN A, FAITATZIADIS S, et al. Robot-assisted radical nephrectomy using the novel avatera robotic surgical system: a feasibility study in a porcine model[J]. J Endourol, 2023, 37(3): 273-278. DOI: 10.1089/end.2022.0596.
    [36] PELEGRIN T, CHAMPY CM, GERBAUD F, et al. Robotic-assisted laparoscopy living donor nephrectomy: technique and results of a monocentric retrospective series[J]. Prog Urol, 2022, 32(8/9): 567-576. DOI: 10.1016/j.purol.2022.03.009.
    [37] KOGA S, YAMANAGA S, HIDAKA Y, et al. Influence of graft ureter length, a donor-related factor, on urinary tract infections after living-donor kidney transplantation: a single-center analysis of 211 cases[J]. Transpl Int, 2022, 35: 10754. DOI: 10.3389/ti.2022.10754.
    [38] FOOTE JB, BIKHET MH, HANSEN-ESTRUCH C, et al. Observations on hydronephrosis after pig kidney transplantation in baboons[J]. Xenotransplantation, 2022, 29(6): e12779. DOI: 10.1111/xen.12779.
  • 加载中
图(4) / 表(1)
计量
  • 文章访问数:  203
  • HTML全文浏览量:  105
  • PDF下载量:  36
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-10-14
  • 录用日期:  2023-12-06
  • 网络出版日期:  2024-01-17
  • 刊出日期:  2024-03-15

目录

    /

    返回文章
    返回