中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (19): 3099-3107.doi: 10.12307/2023.345

• 干细胞综述 stem cell review • 上一篇    

间充质干细胞移植不同的途径可影响肝纤维化治疗效果

马  刚，郑小红，王敬博，韩  英   

  1. 解放军空军军医大学第一附属医院消化内科，陕西省西安市   710000
  • 收稿日期:2022-05-17 接受日期:2022-06-16 出版日期:2023-07-08 发布日期:2022-11-29
  • 通讯作者: 王敬博，博士，副主任医师，硕士生导师，解放军空军军医大学第一附属医院消化内科，陕西省西安市 710000
  • 作者简介:马刚，男，1989年生，安徽省阜阳市人，汉族，解放军空军军医大学在读硕士，主要从事工程化细胞逆转肝纤维化的研究。
  • 基金资助:
    国家重点研发项目(2020YFA0710803)，项目负责人：王敬博

Different transplantation routes of mesenchymal stem cells can affect therapeutic effect on liver fibrosis

Ma Gang, Zheng Xiaohong, Wang Jingbo, Han Ying   

  1. Department of Gastroenterology, First Affiliated Hospital of Air Force Medical University, Xi’an 710000, Shaanxi Province, China
  • Received:2022-05-17 Accepted:2022-06-16 Online:2023-07-08 Published:2022-11-29
  • Contact: Wang Jingbo, MD, Associate chief physician, Master’s supervisor, Department of Gastroenterology, First Affiliated Hospital of Air Force Medical University, Xi’an 710000, Shaanxi Province, China
  • About author:Ma Gang, Master candidate, Department of Gastroenterology, First Affiliated Hospital of Air Force Medical University, Xi’an 710000, Shaanxi Province, China
  • Supported by:
    National Key Research and Development Project, No. 2020YFA0710803 (to WJB)

PDF

23

摘要：


文题释义：

间充质干细胞：是多潜能成体祖细胞，具有向软骨、脂肪、骨髓基质和骨组织分化的能力，其来源广泛，可通过自我更新、多向分化及免疫调节等方式发挥疾病治疗作用。
肝纤维化：是肝细胞长期、反复受致病因素刺激引发的慢性损伤和炎症，主要表现为细胞外基质过度积累，是大多数慢性肝病的共同结果。

背景：间充质干细胞作为肝纤维化的一种有前景的新疗法，治疗作用受多种因素影响，体内移植作为肝纤维化治疗的关键环节，在最佳移植途径的选择上存在争议，优化移植途径对提高间充质干细胞治疗效果尤为重要。
目的：探讨间充质干细胞经不同移植途径治疗肝纤维化的治疗效果。
方法：检索PubMed、中国知网、万方和维普数据库中2007-2021年的相关文献，中文检索词为“间充质干细胞、肝纤维化、移植/输注、途径、机制、生物分布”，英文检索词为“mesenchymal stem cells/stromal cells，liver/hepatic fibrosis/cirrhosis，mechanism，distribution/biodistribution，transplantation route/delivery/engraftment/injection/administration”，排除重复、陈旧或与文章主题不相关文献，对纳入的73篇文献进行总结分析。
结果与结论：①在相同条件下，不同移植途径的间充质干细胞在体内生物分布有差异，受微环境影响可能以不同侧重的抗纤维化机制发挥改善肝纤维化的作用，从而产生不同的治疗纤维化效果。②动物实验研究表明，间充质干细胞治疗肝纤维化移植途径中，经门静脉移植抗纤维化效果与肝动脉等效且不劣于外周静脉移植，脾内移植与外周静脉移植效果相似，且高于肝内移植和腹腔移植；③临床研究表明，肝内移植和脾内移植具有相似的抗纤维化效果，肝动脉移植和门静脉移植效果相当且优于外周静脉移植。④经肝动脉和门静脉移植可能是肝纤维化治疗的最佳途径，经肝内和脾内移植可能因“细胞拥挤”和“短暂清除”限制了干细胞的治疗效果。⑤间充质干细胞治疗肝纤维化移植途径安全有效，选择适合的干细胞移植途径以提高肝组织内干细胞定植量、增强细胞活性、维持干细胞在肝组织内存活时间，可能有利于提高间充质干细胞抗纤维化效果，但不同移植途径下的作用机制尚不明确，临床中不同移植途径的适用指征尚需进一步探讨。
https://orcid.org/0000-0002-0202-3535(马刚)； https://orcid.org/0000-0003-4522-2451(王敬博)
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 间充质干细胞, 肝纤维化, 肝硬化, 移植途径, 生物分布, 机制, 治疗效果, 组织工程

Abstract: BACKGROUND: Mesenchymal stem cell transplantation is a promising new therapy for liver fibrosis, and the treatment effects are affected by many factors. The delivery route of mesenchymal stem cells is a key link in the treatment of liver fibrosis. There is controversy in the selection of the best transplantation route. The transplantation routes are particularly important to improve the treatment effects of mesenchymal stem cells.
OBJECTIVE: To investigate the treatment effects of mesenchymal stem cells in the treatment of liver fibrosis by different transplantation routes.
METHODS: Relevant articles from 2007 to 2021 in PubMed, CNKI, Wanfang and VIP databases were searched. The key words were “mesenchymal stem cells/stromal cells, liver/hepatic fibrosis/ cirrhosis, mechanism, distribution/biodistribution, transplantation route/delivery/engraftment/injection/administration” in Chinese and English, respectively. Repetitive, outdated and irrelevant views were excluded, and the 73 eligible articles were summarized and analyzed.
RESULTS AND CONCLUSION: (1) In the same conditions, the biodistributions of liver mesenchymal stem cells in different transplantation routes were different, and different anti-fibrotic mechanisms may play an important role in improving liver fibrosis in different niches, thus, exerting different treatment effects on fibrosis. (2) Animal experiments have shown that the effects of mesenchymal stem cell transplantation for treating liver fibrosis via intraportal vein are equivalent to that of intrahepatic artery and not inferior to that of intravenous vein, which is higher than intrahepatic and intraperitioneal effects. (3) Clinical studies have shown that intrahepatic and intrasplenic routes have similar treatment effects; intrahepatic artery and intraportal vein have the same effects and superior to the intravenous transplantation. (4) The routes via intrahepatic artery and intraportal vein may be the best way to treat liver fibrosis, and intrahepatic and intrasplenic routes may limit the therapeutic effects of stem cells because of “Cell crowding” and “Transient clearance”. (5) The transplantation routes of mesenchymal stem cells are safe and effective in the treatment of liver fibrosis. It may be beneficial to improve the treatment effects of mesenchymal stem cells to select appropriate approaches to increase stem cell colonization, enhance cell activity, and maintain the survival time of stem cells in liver tissue. It may be beneficial to improve the anti-fibrotic effect of mesenchymal stem cells, but the mechanisms of different transplantation routes are not so far clear, and the indications of different routes need to be further explored.

Key words: mesenchymal stem cell, liver fibrosis, liver cirrhosis, transplantation route, biodistribution, mechanism, treatment effect, tissue engineering

中图分类号: