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间充质干细胞防治慢性移植物抗宿主病:进展与挑战

鲍颖颖, 陈小湧. 间充质干细胞防治慢性移植物抗宿主病:进展与挑战[J]. 器官移植, 2023, 14(3): 327-335. doi: 10.3969/j.issn.1674-7445.2023.03.002
引用本文: 鲍颖颖, 陈小湧. 间充质干细胞防治慢性移植物抗宿主病:进展与挑战[J]. 器官移植, 2023, 14(3): 327-335. doi: 10.3969/j.issn.1674-7445.2023.03.002
Bao Yingying, Chen Xiaoyong. Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges[J]. ORGAN TRANSPLANTATION, 2023, 14(3): 327-335. doi: 10.3969/j.issn.1674-7445.2023.03.002
Citation: Bao Yingying, Chen Xiaoyong. Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges[J]. ORGAN TRANSPLANTATION, 2023, 14(3): 327-335. doi: 10.3969/j.issn.1674-7445.2023.03.002

间充质干细胞防治慢性移植物抗宿主病:进展与挑战

doi: 10.3969/j.issn.1674-7445.2023.03.002
基金项目: 

国家自然科学基金 82270230

国家自然科学基金 81970109

国家重点研发计划 2022YFA1105000

广东省自然科学基金杰出青年项目 2023B1515020119

详细信息
    作者简介:
    通讯作者:

    陈小湧(ORCID:0000-0002-5973-4143),副教授,研究方向为间充质干细胞治疗的细胞与分子机制,Email:chenxiaoy@mail.sysu.edu.cn

  • 中图分类号: R617, R552

Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges

More Information
  • 摘要: 慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植后的主要并发症,也是导致非复发死亡的主要原因,因其病理生理过程复杂,常规糖皮质激素联合免疫抑制药的防治有效率不足50%。对于糖皮质激素抵抗的cGVHD患者需启动二线治疗,然而目前的二线治疗方法尚未形成共识,且治疗效果不佳。间充质干细胞(MSC)是最常见的成体干细胞之一,因其具有多维度、多靶点的免疫调控功能,已被广泛应用于cGVHD的预防及治疗,且大量研究证实了MSC治疗cGVHD的安全性和有效性,有望成为cGVHD防治的新策略。本文主要围绕MSC防治cGVHD的研究进展、作用机制及存在的问题等方面进行综述,以期为今后优化MSC治疗方案、提高cGVHD防治效果提供新思路。

     

  • 图  1  cGVHD主要发病环节

    注:→表示促进或进展,┥表示抑制,×表示阻断。GC为生发中心。

    Figure  1.  Overview of cGVHD pathogenesis

    表  1  MSC预防cGVHD的临床现状

    Table  1.   The clinical status of MSC in prevention of cGVHD

    研究者 年份(年) 患者类型 MSC组(n)/对照组(n) MSC来源 MSC剂量(×106/kg) 结论
    Liu, et al[10] 2011 成人、儿童 27/28 骨髓 0.30~0.50 两组间2年生存率及复发率差异无统计学意义;MSC组cGVHD发生率有所降低;血浆中SDF-1α、TPO、IL-11升高
    Gao, et al [13] 2016 成人、儿童 62/62 脐带 不详 MSC治疗组cGVHD累积发生率显著降低;2年生存率差异无统计学意义;Treg及CD27+记忆性B细胞数量增加
    Wang, et al [14] 2021 成人 17/0 骨髓 0.01~65.00 MSC治疗后5年生存率为64.7%,非复发性生存率为79.1%;2年cGVHD的发生率为63%,中度及重度cGVHD的发生率为17%
    Zhao, et al [15] 2022 成人、儿童 99/99 骨髓 1.00 MSC治疗组1年和2年cGVHD的累积发生率显著低于对照组
    Wang, et al [20] 2019 儿童 35/0 骨髓 1.00 MSC治疗后所有患者均实现造血重建,总生存率为85.71%,cGVHD的发生率为22.86%
    注:①SDF为基质细胞衍生因子。
    ②TPO为促血小板生成素。
    下载: 导出CSV

    表  2  MSC治疗cGVHD的临床现状

    Table  2.   The clinical status of MSC treatment for cGVHD

    研究者 年份(年) 患者类型 n MSC来源 MSC剂量(×106/kg) 结论
    Macías-Sánchez, et al [9] 2022 成人、儿童 16 骨髓,脂肪 0.52~2.10 MSC反应良好者2年生存率达70.00%,无应答者生存率为16.67%;18岁以下患者2年生存率更高
    Weng, et al[22] 2010 成人 19 骨髓 0.23~1.42 对MSC的治疗反应良好的患者达73.7%,2年生存率达到77.7%;MSC治疗组CD5+CD19+B细胞比例增加,CD8+CD28+T细胞比例降低
    Jurado, et al [23] 2017 成人 14 脂肪 1.00或3.00 完全缓解的患者达80.0%;未见基础疾病复发及感染造成的死亡;总生存率为71.4%
    Boberg, et al [24] 2020 成人 11 骨髓 1.30~3.00 6例患者严重的cGVHD症状得到持续改善;MSC反应良好者免疫抑制药减量或停用;MSC能够改善患者的胸腺功能,初始Treg比例增加
    Peng, et al [27] 2014 成人 38 骨髓 1.00 5例患者完全缓解,23例患者部分缓解;血浆BAFF水平降低;CD27+记忆B细胞增加
    Peng, et al [28] 2015 成人 23 骨髓 1.00 20例患者出现完全缓解或部分缓解;复发率和病死率与其他治疗间差异无统计学意义;MSC反应良好者CD5+IL-10+B细胞比例显著上升
    Stenger, et al [29] 2022 成人 7 骨髓 2.00 3个不同剂量MSC输注均耐受性良好;7例cGVHD中有5例部分缓解,外周血淋巴细胞亚群差异无统计学意义
    注:①BAFF为B细胞活化因子。
    下载: 导出CSV
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  • 收稿日期:  2023-01-16
  • 刊出日期:  2023-05-15

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