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神经细胞异种移植的研究进展

张青 周翠冰 戴一凡 蔡志明 牟丽莎

张青, 周翠冰, 戴一凡, 等. 神经细胞异种移植的研究进展[J]. 器官移植, 2017, 8(4): 328-332. doi: 10.3969/j.issn.1674-7445.2017.04.017
引用本文: 张青, 周翠冰, 戴一凡, 等. 神经细胞异种移植的研究进展[J]. 器官移植, 2017, 8(4): 328-332. doi: 10.3969/j.issn.1674-7445.2017.04.017

神经细胞异种移植的研究进展

doi: 10.3969/j.issn.1674-7445.2017.04.017
基金项目: 

深圳市三名工程 2014

深圳市科创委学科布局项目 JCYJ20160229204849975

深圳市高水平医学学科建设专项基金 2016031638

深圳市科技研发资金基础研究—自由探索 JCYJ20160425104534335

深圳市科创委企业工程中心项目 GCZX2015043017281705

深圳市科创委基础研究自由探索项目 201703063000044

中国博士后科学基金 2017M612790

详细信息
    通讯作者:

    牟丽莎, Email:molly__molly@163.com

  • 中图分类号: R322.81

  • 摘要: 神经细胞移植为神经退行性紊乱疾病的有效治疗手段之一。然而, 目前用于帕金森病和亨廷顿舞蹈症的人体胚胎源神经细胞治疗策略因疗效、胚胎组织来源及伦理问题等难以广泛应用于临床。猪源细胞移植应运而生, 然而受异种移植细胞来源、免疫排斥反应和临床治疗策略等的限制, 目前仍处于研究阶段。本文就猪源神经细胞和灵长类神经细胞的异种移植研究进展作一综述。

     

  • 表  1  猪来源神经异种移植的研究现状

    Table  1.   Current status of xenotransplantation of swine derived nerve

    研究模型 移植受体 移植物 移植后功能评估 小结
    PD[7-8] 大鼠 猪腹侧中脑细胞 存活; 6周内分化[9]; 8周后恢复功能[10] 移植后神经功能有一定恢复, 移植细胞可能通过神经保护和神经修复因子的分泌来介导神经功能的改善[11]
    PD[7-8] 大鼠 猪源干细胞体外分化的神经 3个月内移植物存活
    SCI[7-8] 大鼠 猪源干细胞及其分化神经前体 6个月内移植物分化和功能改善
    PD 灵长类动物 猪神经 12周检测到猪神经异种移植物[12]; 神经功能恢复情况未知 神经功能评估得以改善, 移植物死后猪大脑存在大量多巴胺能、血清素能和GABA能分化的神经元和神经胶质细胞
    PD 灵长类尾状核 封装的猪脉络丛细胞 4周出现旋转行为; 神经功能的稳定恢复可达6个月; 植入纹状体内检测到自体TH+纤维
    PD 灵长类动物 WT和hCTLA4-IgG猪腹侧中脑[13] 重要自主运动恢复(1~30个月)
    PD 12例患者 猪腹侧中脑细胞 3例患者重要临床改善( > 基线分30%), 保持稳定状态12个月[5]; 移植后7.5个月患者体内猪多巴胺能神经元存活[14] 观察到的行为学改善与氟-PET信号的恢复无直接相关; 猪胚胎神经移植在HD患者体内无明显改善作用
    HD 12例患者 猪胚胎神经组织 临床表现无显著改善[15]
      WT为野生型; hCTLA4-IgG为人细胞毒性T淋巴细胞相关抗原4免疫蛋白; GABA为γ-氨基丁酸; TH为酪氨酸羟化酶; PET为正电子发射型计算机断层显像
    下载: 导出CSV

    表  2  非人灵长类动物用于神经退行性疾病体内研究的优势分析

    Table  2.   Advantages analysis of nonhuman primates in the study of neurodegenerative diseases in vivo

    优势 可行性分析
    大脑体积大 复杂的细胞整合和更长轴突的评估研究; 神经传递过程
    大脑解剖结构 1.与人类相似:复杂的回路和连接; 皮层抑制神经递质基因下调前额皮质, 与推理、抑制、计划能力相关的大脑功能性区域[35]; 认知测试及进步的评估2.与鼠类不同:基底神经节和黑质中多巴胺神经元[36]; 衰老老鼠无皮层抑制神经递质基因[37]
    免疫调控策略 啮齿类动物中成功的策略不一定适用于灵长类动物
    长寿 动物模型的长寿决定了对其较长的跟踪期, 可实现对神经细胞分化和退化过程的长期监控
    视觉刺激控制行为 与人类相似
    下载: 导出CSV

    表  3  人类神经干细胞异种移植研究现状

    Table  3.   Current status of xenotransplantation of human neural stem cells

    移植物 移植受体 移植效果
    人神经干细胞 灵长类动物的脑实质 神经分化和长期生存可长达24个月[18]
    人体心室生发区来源的未分化人体胚胎细胞 灵长类动物 有帕金森症状者功能恢复, 存活并迁移, 可长达7个月[38]; 分化为多巴胺能神经纤维, 表达GDNF[25]
    体外胚胎干细胞 尾状核和黑质 中脑多巴胺能分化神经元长达2个月, 具有移植轴突延长生长能力[27]
    基因转染GDNF载体的神经皮质祖细胞 年老非人灵长类 GDNF的传递有所尝试[39]
    人神经干细胞 灵长类动物(EAE) 体内存留3个月, 疾病症状减轻[40]
    人神经干细胞 大鼠急性腰椎脊髓损伤模型 减轻马达感知紊乱和强直状态[41]
    人胚胎神经干细胞 后脑辐照的大鼠 认知功能提高[42]
      EAE为自身免疫性脑脊髓炎; GDNF为胶质细胞源性神经营养因子
    下载: 导出CSV
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出版历程
  • 收稿日期:  2017-05-01
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2017-07-15

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