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中华移植杂志(电子版) ›› 2022, Vol. 16 ›› Issue (03) : 183 -189. doi: 10.3877/cma.j.issn.1674-3903.2022.03.011

综述

异种心脏移植基因修饰策略及围手术期管理研究进展
任明仕1, 王嵘2,(), 王明岩2, 张丽月1, 成楠2, 吴远斌1   
  1. 1. 100039 北京,中国人民解放军总医院第六医学中心心血管外科;100039 北京,解放军医学院
    2. 100039 北京,中国人民解放军总医院第六医学中心心血管外科
  • 收稿日期:2022-05-24 出版日期:2022-06-25
  • 通信作者: 王嵘
  • 基金资助:
    国家重点专项研发计划(2019YFA0110704)

The research progress in gene modification strategies and perioperative management of cardiac xenotransplantation

Mingshi Ren1, Rong Wang2,(), Mingyan Wang2, Liyue Zhang1, Nan Cheng2, Yuanbin Wu1   

  1. 1. Division of Cardiac Surgery, Department of Cardiology, the Sixth Medical Center, Chinese PLA General Hospital, Beijing 100039, China; Medical School of Chinese PLA, Beijing 100039, China
    2. Division of Cardiac Surgery, Department of Cardiology, the Sixth Medical Center, Chinese PLA General Hospital, Beijing 100039, China
  • Received:2022-05-24 Published:2022-06-25
  • Corresponding author: Rong Wang
引用本文:

任明仕, 王嵘, 王明岩, 张丽月, 成楠, 吴远斌. 异种心脏移植基因修饰策略及围手术期管理研究进展[J]. 中华移植杂志(电子版), 2022, 16(03): 183-189.

Mingshi Ren, Rong Wang, Mingyan Wang, Liyue Zhang, Nan Cheng, Yuanbin Wu. The research progress in gene modification strategies and perioperative management of cardiac xenotransplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 183-189.

异种心脏移植(CXTx)为解决终末期心衰患者心脏移植供器官短缺提供了广阔的发展前景,是缓解供心短缺的可行策略。人源化基因修饰技术的进步为CXTx临床应用翻开了新篇章。CXTx动物模型的建立为解决异种排斥反应探索出一条可行的技术路线,显著延长移植器官存活时间。本文综述近年来异位和原位CXTx的研究进展,并从多项前瞻性临床前研究的数据中筛选出部分相关数据进行分析,探讨CXTx动物模型的构建策略及可能优化的治疗方案,以期为临床提供借鉴。

Cardiac xenotransplantation (CXTx) offers a promising development to address the shortage of donor organs for patients with end-stage heart failure and is a viable strategy to alleviate the shortage of donor hearts. The progress of humanized gene modification technology has opened a new chapter for the clinical application of xenotransplantation.The establishment of animal model of cardiac xenotransplantation has explored a feasible technical route to solve the xenorejection reaction and significantly extended the survival time of transplanted organs.This review will discuss the recent research results of ectopic and orthotopic cardiac xenotransplantation, and some relevant data were selected from several prospective preclinical studies for analysis to explore the construction strategy of heterotopic heart transplantation model and the possible optimal treatment plan, to provide reference for clinic.

表1 不同中心基因编辑猪-非人灵长类动物异种心脏移植免疫抑制及生命支持方案
文献 免疫诱导方案 免疫抑制维持方案 其它支持治疗方案 受体存活情况(d)
Kuuaki等[47] ATG(50 mg/kg) 抗人CD154单抗(25 mg/kg) 阿司匹林[40 mg(隔日)] 最长存活78
  LoCD2b(1~4 mg/kg) 抗CD40单抗(20~25 mg/kg) 肝素(5~60 U·kg-1·h-1)  
  胸腺照射(700 cGy) MMF(25~110 mg/kg) 更昔洛韦(5 mg·kg-1·d-1)  
  眼镜蛇毒因子(6 mg/d) 甲泼尼龙(4.0~0.5 mg/kg) 左氧氟沙星(10 mg·kg-1·d-1)  
Bauer等[61] TPC(50 mg/kg) 他克莫司(剂量未说明)   最长存活50
  Ati-CD2b(1~4 mg/kg) 西罗莫司(剂量未说明)    
    MMF(25~110 mg/kg)    
    甲泼尼龙(逐渐减量,剂量未说明)    
Mcgregor等[41] TPC(50 mg/kg) 他克莫司(血药浓度维持在20~30 ng/mL)   96(15,37)
  利妥昔单抗(19 mg/kg,每周) 西罗莫司(血药浓度维持在20~30 ng/mL)    
  甲泼尼龙(逐渐减量,剂量未说明)      
Mohiuddin等[27] ATG(5 mg/kg) 抗CD40单抗(10~50 mg/kg)/抗CD40单抗(20~50 mg/kg) EPO(200 U/kg) 70(21,236)
  利妥昔单抗(19 mg/kg,每周) MMF(20 mg/kg,2次/d) 肝素(50~400 U/h)  
  眼镜蛇毒因子(6 mg/d) 甲泼尼龙(逐渐减量,剂量未说明) 更昔洛韦(5 mg·kg-1·d-1)  
      头孢唑林钠(250 mg/kg,2次/d,共7 d)  
Mohiuddin等[33] ATG(5 mg/kg) 抗CD40(10~50 mg/kg) EPO(200 U/kg) 298(159,945)
  抗CD20b单抗(19 mg/kg) 阿司匹林(81 mg) 肝素(50~400 U/h)  
  抗CD40b单抗(50 mg/kg) MMF(20 mg/kg) 更昔洛韦(5 mg·kg-1·d-1)  
    甲泼尼龙(2 mg/kg,逐渐减量) 头孢唑林钠(250 mg/kg,2次/d,共7 d)  
Längin等[2] ATG(5 mg/kg) 抗CD40(50 mg/kg) 低分子肝素(20~40 U·kg-1·h-1) 195(159,945)
  抗CD2b(19 mg/kg) MMF(40 mg/kg) EPO[2 000 U(移植前第7天及移植当天各应用1次)]  
  抗CD40b(50 mg/kg) 甲泼尼龙(10 mg/kg,逐渐减量) 更昔洛韦(5 mg·kg-1·d-1)  
    雷帕霉素(血药浓度维持在5~10 ng/mL) 头孢唑林钠(250 mg/kg,2次/d,共7 d)  
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