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走向临床的异种器官移植

孙圣坤, 杨树军, 卫浩, 等. 走向临床的异种器官移植[J]. 器官移植, 2024, 15(2): 200-206. doi: 10.3969/j.issn.1674-7445.2023234
引用本文: 孙圣坤, 杨树军, 卫浩, 等. 走向临床的异种器官移植[J]. 器官移植, 2024, 15(2): 200-206. doi: 10.3969/j.issn.1674-7445.2023234
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

走向临床的异种器官移植

doi: 10.3969/j.issn.1674-7445.2023234
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),Email:sunshengkun@301hospital.com.cn;彭江(ORCID 0000-0003-4662-9288),主任医师,教授,博士研究生导师,研究方向为股骨头坏死保髋治疗、关节软骨损失修复、周围神经损失修复及骨科康复治疗,Email: pengjiang301@126.com

  • 中图分类号: R617, Q78

Application of xenotransplantation in clinical practice

More Information
  • 摘要: 器官移植是治疗终末期器官衰竭的最佳方案,但器官短缺是全球性的问题,限制了器官移植的进一步发展。最新的研究表明,基因修饰猪可能很快成为临床器官移植供体的现实替代来源。异种移植可能是解决器官短缺问题的有效途径之一。2021年以来,全世界完成了2例活体异种器官移植、6例脑死亡异种器官移植,并启动了异种肾移植的Ⅰ期临床试验,取得了超出预期的结果。因此,本文在回顾、分析近几年活体及脑死亡受者异种移植临床试验结果的基础上,讨论与异种移植临床研究相关的科学、技术和伦理问题,希望为我国异种器官移植临床研究提供借鉴,促进临床异种移植的发展。

     

  • FIG. 2989.  FIG. 2989.

    FIG. 2989..  FIG. 2989.

    表  1  过去3年的活体及脑死亡受者异种移植临床试验

    Table  1.   Clinical trial of xenotransplantations in living and brain death recipients in the past 3 years

    研究单位 手术时间 供体猪基因编辑方案 移植
    器官
    受者 免疫调节方案 预后结果
    马里兰大学医学院[3-4] 2023年
    9月20日
    10基因编辑 心脏 男性,58岁,晚期心力衰竭患者 抗CD154抗体+常规抗排斥药物 术后第1个月无任何排斥反应,术后40 d因排斥反应死亡
    纽约大学朗格尼移植研究所[5] 2023年
    7月14日
    GGTA1单基因敲除 肾脏 男性,58岁,脑死亡,死亡原因为脑肿瘤 _ 观察61 d后切除肾脏,尽管出现短暂的排斥反应,但移植肾正常工作
    纽约大学朗格尼移植研究所[6] 2022年
    7月6日
    10基因编辑 心脏 女性,64岁,脑死亡,既往2次器官移植病史(肾、胰腺) 诱导:ATG+甲泼尼龙+依库珠单抗;维持:甲泼尼龙+吗替麦考酚酯 术后监测66 h。移植后立即表现出良好的心功能,并在研究期间功能良好。心内膜心肌活组织检查未发现细胞或抗体介导的排斥反应,无人畜共患病传播的证据
    纽约大学朗格尼移植研究所[6] 2022年
    6月16日
    10基因编辑 心脏 男性,72岁,脑死亡 诱导:ATG+甲泼尼龙+依库珠单抗;维持:甲泼尼龙+吗替麦考酚酯 术后监测66 h。供体猪和受者尺寸不匹配,术后心功能下降
    阿拉巴马大学[7] 2022年4月22日首次公布,2023年9月1日更新 10基因编辑 肾脏 尚无入选 诱导:ATG+甲泼尼龙+依库珠单抗;维持:他克莫司+吗替麦考酚酯+泼尼松+依库珠单抗 Ⅰ期临床试验。2023年9月1日还未招募,预计2024年1月开始,2028年6月初步完成,2029年6月研究结束
    马里兰大学医学院[8-10] 2022年
    1月7日
    10基因编辑 心脏 男性,57岁,活体,非缺血性心肌病,依赖体外膜肺氧合生存 利妥昔单抗+ATG+补体C1抑制剂+KPL-404+吗替麦考酚酯(最终因中性粒细胞减少而改为他克莫司) 术后49 d移植心脏开始膨胀并逐渐衰竭。术后60 d因移植失败死亡。无明显排斥反应。尸检所有受者器官均检测到猪巨细胞病毒或猪玫瑰病毒DNA和猪细胞DNA
    阿拉巴马大学[11] 2021年 10基因编辑 肾脏 男性,57岁,外伤后脑死亡,移植前双肾切除,植入猪的双肾 诱导:甲泼尼龙+ATG+抗CD20单抗;维持:吗替麦考酚酯+他克莫司+泼尼松 肾脏存活74 h,产生尿液但血清肌酐未下降。未检测到猪病毒。术后1 d出现弥漫性血栓性微血管病,但术后3 d没有证据显示出现皮质坏死或间质出血
    纽约大学朗格尼移植研究所[12-13] 2021年
    11月22日、2021年
    9月25日
    GGTA1单基因敲除 肾脏
    接入
    股动
    静脉
    2例脑死亡患者,肾脏未切除 吗替麦考酚酯+甲泼尼龙 观察54 h,期间持续产生尿液,估算肾小球滤过率增加,血清肌酐下降,活组织检查未发生超急性排斥反应及抗体介导的排斥反应,移植肾每小时产生尿量是自体肾脏的2倍。受体未检测到猪内源性逆转录病毒。但2023年9月30日,该团队在Lancet发文,多模态深度表型分析显示,早期存在抗体介导的排斥反应
      注:①GGTA1为α-1, 3-半乳糖基转移酶。
        ②为原文未提及。
        ③ATG为抗胸腺细胞球蛋白。
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-11-05
  • 网络出版日期:  2023-12-25
  • 刊出日期:  2024-03-15

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