中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (19): 3091-3098.doi: 10.12307/2023.633

• 干细胞综述 stem cell review • 上一篇    

干细胞对肝脏疾病的临床治疗前景与研究现状

黄贵才1，罗业浩1，江慧容1，李  媛2，毛德文2，官志杰2   

  1. 1广西中医药大学，广西壮族自治区南宁市   530200；2广西中医药大学第一附属医院肝病科，广西壮族自治区南宁市   530023
  • 收稿日期:2022-04-15 接受日期:2022-08-25 出版日期:2023-07-08 发布日期:2022-11-29
  • 通讯作者: 官志杰，副主任医师，硕士生导师，广西中医药大学第一附属医院肝病科，广西壮族自治区南宁市 530023
  • 作者简介:黄贵才，男，1995年生，广西壮族自治区人，汉族，广西中医药大学在读硕士，主要从事肝脏疾病研究。
  • 基金资助:
    国家自然科学基金项目(81774236)，项目负责人：毛德文

Clinical therapeutic prospect and current research status of stem cells for liver diseases

Huang Guicai1, Luo Yehao1, Jiang Huirong1, Li Yuan2, Mao Dewen2, Guan Zhijie2   

  1. 1Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China; 2Department of Hepatology, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, Guangxi Zhuang Autonomous Region, China
  • Received:2022-04-15 Accepted:2022-08-25 Online:2023-07-08 Published:2022-11-29
  • Contact: Guan Zhijie, Associate chief physician, Master’s supervisor, Department of Hepatology, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, Guangxi Zhuang Autonomous Region, China
  • About author:Huang Guicai, Master candidate, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 81774236 (to MDW)

PDF

89

摘要：


文题释义：

干细胞：是具有多向分化潜能、自我更新能力的细胞，是处于细胞系起源顶端的最原始细胞，在体内能够分化产生某种特定组织类型的细胞。
肝脏疾病：是发生在肝脏的所有疾病的总称，包括感染性疾病、肿瘤性疾病、血管性疾病、代谢性疾病、中毒性疾病、自身免疫性疾病及遗传性疾病等。

背景：干细胞在肝脏的再生与自我修复能力中发挥着重要的作用，对于肝脏疾病的临床诊断和治疗具有重要意义。
目的：总结目前国内外该领域的临床试验及基础研究，回顾以往治疗肝脏疾病的干细胞类型，各类干细胞对各类肝脏疾病的治疗方案，概述各类干细胞对肝脏疾病未来应用的临床应用前景，为其应用于临床肝脏疾病的治疗提供研究基础。
方法：应用计算机以“stem cells，mesenchymal stem cell，hepatic stem cell，embryonic stem cell，induced pluripotent stem cell，hematopoietic stem cell，hepatopathy，non-alcoholic fatty liver disease，liver cirrhosis，liver failure，autoimmune hepatitis，hepatocellular carcinoma”为检索词，检索PubMed、Web of Science及Wiley电子期刊数据库中的相关文献，根据纳入标准并筛选，最终选择71篇文献进行综述。
结果与结论：①对于治疗肝脏疾病的干细胞主要以间充质干细胞、肝脏干细胞、胚胎干细胞、诱导性多能干细胞及造血干细胞等为主，文章总结归纳了上述干细胞的特点、表达的时期以及在肝脏受损后分化的应用情况。②综合来看，间充质干细胞可通过外泌体、基质金属蛋白酶、抗炎症反应等修复肝脏；肝脏干细胞可通过分化肝卵圆细胞和小肝细胞样祖细胞最终形成成熟的肝细胞，促进肝脏损伤修复；诱导性多能干细胞、胚胎干细胞和造血干细胞可通过迅速的增殖与分化，转换为成熟的肝细胞。③干细胞对于各种肝脏疾病的治疗，主要通过诱导内源性细胞增殖、免疫调节、抑制炎症生成、促肝细胞再生以及修复受损组织来实现。④综合而言，目前间充质干细胞获取相对容易，应用前景最广，而且并不涉及伦理问题，正在实现由临床前研究到临床研究的转化。由于间充质干细胞可分化为各种成体干细胞、免疫原性低、自我增殖和分化能力强等优势，特别对于治疗免疫性肝炎、肝硬化及肝细胞癌等肝脏疾病效果最为理想。⑤诱导性多能干细胞因其可分化成特异性体细胞和肝细胞，且无免疫排斥反应，对于治疗终末期肝病效果更为显著。⑥然而，干细胞移植后可出现腹泻、黄疸及皮疹等急性排斥反应，供受者间的组织相容性差则容易导致移植物抗宿主反应等不良反应，所以干细胞移植后对于干细胞的应用及其临床安全性的评估，仍需要更多的临床试验以及循证医学数据的支持。
https://orcid.org/0000-0002-2959-7598 (黄贵才)；https://orcid.org/0000-0003-1298-5022(官志杰)

关键词: 干细胞, 间充质干细胞, 诱导性多能干细胞, 肝脏疾病, 肝硬化, 肝细胞癌, 临床治疗, 综述

Abstract: BACKGROUND: Stem cells play an important role in liver regeneration and self-repair ability, which is of great significance for clinical diagnosis and treatment of liver diseases.  
OBJECTIVE: To summarize the current clinical trials and basic research in this field in and outside China, review the types of stem cells used to treat liver diseases in the past, and the treatment programs of various types of stem cells for various types of liver diseases, outline the clinical application prospects of various types of stem cells in the future application of liver diseases, and provide a research basis for the treatment of clinical liver diseases.
METHODS: Using “stem cells, mesenchymal stem cells, hepatic stem cell, embryonic stem cell, induced pluripotent stem cell, hematopoietic stem cell, hepatopathy, non-alcoholic fatty liver disease, liver cirrhosis, liver failure, autoimmune hepatitis, hepatocellular carcinoma” as search words, the relevant articles in PubMed, Web of Science and Wiley e-journal databases were searched, and 71 articles were selected for review according to the inclusion criteria.  
RESULTS AND CONCLUSION: (1) Mesenchymal stem cells, liver stem cells, embryonic stem cells, induced pluripotent stem cells and hematopoietic stem cells are the main stem cells for the treatment of liver diseases. The characteristics, expression period and application of these stem cells in differentiation after liver injury are summarized in this paper. (2) In general, mesenchymal stem cells can repair liver through exosomes, matrix metalloproteinase and anti-inflammatory response. Liver stem cells can differentiate liver oval cells and small hepatocellular progenitor cells to form mature liver cells and promote liver injury repair.  Induced pluripotent stem cells, embryonic stem cells and hematopoietic stem cells can transform into mature hepatocytes through rapid proliferation and differentiation. (3) The treatment of various liver diseases by stem cells is mainly achieved by inducing endogenous cell proliferation, immune regulation, inhibiting inflammation, promoting liver cell regeneration and repairing damaged tissues. (4) On the whole, at present, mesenchymal stem cells are relatively easy to obtain, have the broadest application prospects, and do not involve ethical issues. They are transforming from preclinical research to clinical research. Because mesenchymal stem cells can differentiate into various adult stem cells, they have the advantages of low immunogenicity, strong self-proliferation and differentiation ability. Especially for the treatment of immune hepatitis, liver cirrhosis and hepatocellular carcinoma and other liver diseases, mesenchymal stem cells have the most ideal effect. (5) Induced pluripotent stem cells are more effective in the treatment of end-stage liver disease because they can differentiate into specific somatic cells and hepatocytes without immune rejection. (6) However, stem cell transplantation can induce acute rejection, such as diarrhea, jaundice, and skin rashes. Poor histocompatibility between donors and recipients can easily lead to adverse reactions such as graft-versus-host reactions. After stem cell transplantation, the use of stem cells and its clinical safety assessment still need the support of more clinical trials and evidence-based medicine data.

Key words: stem cell, mesenchymal stem cell, induced pluripotent stem cell, liver disease, liver cirrhosis, hepatocellular carcinoma, clinical treatment, review

中图分类号: