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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2020, Vol. 10 ›› Issue (06) : 373 -377. doi: 10.3877/cma.j.issn.2095-1221.2020.06.010

所属专题： 文献；

综述

肝细胞生长因子基因修饰的间充质干细胞治疗肝损伤的研究进展
修文丽1, 毛成刚1, 杨晨宇1, 董蒨1,†()   
  1. 1. 266003　青岛大学附属医院小儿外科　山东省数字医学与计算机辅助手术重点实验室　山东省数字医学临床治疗与营养健康协同创新中心
  • 收稿日期:2020-02-28 出版日期:2020-12-01
  • 通信作者: 董蒨
  • 基金资助:
    山东省青岛市科技攻关项目(20-4-1-5-nsh); 山东省自然科学基金(ZR2017PH040)

Mesenchymal stem cells modified with hepatocyte growth factor gene in the treatment of liver injury

Wenli Xiu1, Chenggang Mao1, Chenyu Yang1, Qian Dong1,†()   

  1. 1. Department of Pediatric Surgery, the Affiliated Hospital of Qingdao University, Shandong Provincial Key Laboratory of Digital Medicine and Computer-assisted Surgery, Shandong College Collaborative Innovation Center of Digital Medicine Clinical Treatment and Nutrition Health, Qingdao 266003, China
  • Received:2020-02-28 Published:2020-12-01
  • Corresponding author: Qian Dong
  • About author:
    Corresponding author: Dong Qian, Email:
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修文丽, 毛成刚, 杨晨宇, 董蒨. 肝细胞生长因子基因修饰的间充质干细胞治疗肝损伤的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2020, 10(06): 373-377.

Wenli Xiu, Chenggang Mao, Chenyu Yang, Qian Dong. Mesenchymal stem cells modified with hepatocyte growth factor gene in the treatment of liver injury[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(06): 373-377.

减轻肝脏损伤、促进肝脏修复和再生始终是肝脏疾病研究中的重点。间充质干细胞（MSCs）是众多具有组织修复和再生能力细胞中的明星细胞，合成的多种细胞因子经旁分泌途径发挥调控细胞生存，调节炎症反应，促进血管再生和减轻纤维化等多种生物学效应，肝细胞生长因子（HGF）便是重点细胞因子之一。基于HGF的信号调控作用，再结合MSCs的干细胞优势，HGF基因修饰间充质干细胞（HGF-MSCs）作为一种干细胞治疗新策略能够发挥"1+1>2"的效果。本文就HGF-MSCs在减轻和修复肝损伤中的研究进展作综述。

关键词: 间充质干细胞, 肝细胞生长因子, 肝损伤

Liver disease research has always focused on reducing the injury and promoting the repair and liver regeneration. Mesenchymal stem cells (MSCs) are useful for tissue repair and regeneration. MSCs synthesize various cytokines to regulate cell survival, inflammatory response, promote angiogenesis, and reduce fibrosis through a paracrine manner. Hepatocyte growth factor (HGF) is one of those cytokines with the signaling regulation effect, and MSCs modified with HGF gene (HGF-MSCs) as a new stem cell therapy strategy can play agreat role. This review provides insight into the advantages of HGF-MSCs in mitigating and repairing liver injury.

Key words: Mesenchymal stem cells, Hepatocyte growth factor, Liver injury
图1 HGF-MSC治疗肝损伤
1
薛改. 脐带间充质干细胞对肝损伤的治疗作用及其机制研究[D]. 石家庄:河北医科大学, 2017.
2
董蒨, 周显军. 计算机辅助手术系统指导小儿肝脏肿瘤精准手术[J]. 临床小儿外科杂志, 2017, 16(6):533-536.
3
Zhao J, Zhou XJ, Zhu CZ, et al. 3D simulation assisted resection of giant hepatic mesenchymal hamartoma in children[J]. Comput Assist Surg (Abingdon), 2017, 22(1):54-59.
4
Ren G, Chen X, Dong F, et al. Concise review: mesenchymal stem cells and translational medicine: emerging issues[J]. Stem Cells Transl Med, 2012, 1(1):51-58.
5
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy, 2006, 8(4):315-317.
6
丁爱兴, 禹亚彬, 黄庆峰, 等. 间充质干细胞在肝再生研究中的应用[J]. 中华肝胆外科杂志, 2013, 19(7):556-558.
7
Aquino JB, Bolontrade MF, Garcia MG, et al. Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma[J]. Gene Ther, 2010, 17(6):692-708.
8
Yannaki E, Athanasiou E, Xagorari A, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs[J]. Exp Hematol, 2005, 33(1):108-119.
9
Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis[J]. Liver Transpl, 2009, 15(5):484-495.
10
Yin S, Ji C, Wu P, et al. Human umbilical cord mesenchymal stem cells and exosomes: bioactive ways of tissue injury repair[J]. Am J Transl Res, 2019, 11(3):1230-1240.
11
Abbaszadeh H, Ghorbani F, Derakhshani M, et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm[J]. J Cell Physiol, 2020, 235(2):706-717.
12
高小月, 张玉泉, 杨晓清. 人脐带间充质干细胞在组织损伤修复中的研究进展[J]. 生物医学工程与临床, 2018, 22(2):208-213.
13
赵贵芳. 脐带间充质干细胞及其来源外泌体修复皮肤损伤的机制研究[D]. 长春:吉林大学, 2016.
14
Nakamura T, Nawa K, Ichihara A. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats[J]. Biochem Biophys Res Commun, 1984, 122(3): 1450-1459.
15
Mars WM, Liu ML, Kitson RP, et al. Immediate early detection of urokinase receptor after partial hepatectomy and its implications for initiation of liver regeneration[J]. Hepatology, 1995, 21(6):1695-1701.
16
Nakagami H, Morishita R, Yamamoto K, et al. Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK, STAT3, and AKT in endothelial cells[J]. Hypertension, 2001, 37(2 Pt 2):581-586.
17
董薇. 肝细胞生长因子及其临床应用研究进展[J]. 微生物学免疫学进展, 2001, 29(3):87-91.
18
Gherardi E, Stoker M. Hepatocytes and scatter factor[J]. Nature, 1990, 346(6281):228.
19
Higashio K, Shima N, Goto M, et al. Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor[J]. Biochem Biophys Res Commun, 1990, 170(1):397-404.
20
韩振国, 闫继东, Jiang WG. 肝细胞生长因子对肺癌细胞运动和侵袭的影响及原癌基因C-met的表达[J]. 中国免疫学杂志, 1997, 13(5):280-282.
21
沈蓉蓉, 郑筱娇, 赵行, 等. 肝细胞生长因子抑制肿瘤细胞凋亡作用研究[J]. 中国药学杂志, 2012, 47(18):1478-1482.
22
许烂漫, 何进科, 张天晓, 等. 骨髓间充质干细胞免疫调节作用对急性肝功能衰竭大鼠肝再生的影响[J]. 中华传染病杂志, 2016, 34(2):97-102.
23
王荣, 邓运涛, 陈强. 人脐带间充质干细胞分泌肝细胞生长因子的初步研究[J]. 中国输血杂志, 2014, 27(8):825-829.
24
Zhang J, Zhou S, Zhou Y, et al. Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model[J]. PLoS One, 2014, 9(12):e114670.
25
Jang YH, You DH, Nam MJ. Protective effects of HGF gene-expressing human mesenchymal stem cells in acetaminophen-treated hepatocytes[J]. Growth Factors, 2015, 33(5-6):319-325.
26
Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration[J]. Mol Ther, 2007, 15(7):1382-1389.
27
Hang H, Yu Y, Wu N, et al. Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4alpha transduction[J]. PLoS One, 2014, 9(8):e104133.
28
Choi YJ, Lee CM, Lee JH, et al. Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide-induced apoptosis in mesenchymal stem cells[J]. Environ Toxicol, 2019, 34(11):1236-1245.
29
潘兴南, 魏开鹏. 肝细胞生长因子的浓度和诱导时间对人骨髓间充质干细胞向肝细胞分化的影响[J]. 肝脏, 2013, 18(6):382-385.
30
Bonefeld K, Moller S. Insulin-like growth factor-I and the liver[J]. Liver Int, 2011, 31(7):911-919.
31
潘丽娟, 王荣丽. 白细胞介素1β联合肝细胞生长因子体外培养骨髓间充质干细胞向肝细胞样细胞的分化[J]. 中国组织工程研究, 2019, 23(33): 5328-5333.
32
Zuo L, Hemmelgarn BT, Chuang CC, et al. The role of oxidative stress-induced epigenetic alterations in amyloid-beta production in Alzheimer's Disease[J]. Oxid Med Cell Longev, 2015, 2015:604-658.
33
Moon SH, Lee CM, Park SH, et al. Effects of hepatocyte growth factor gene-transfected mesenchymal stem cells on dimethylnitrosamine-induced liver fibrosis in rats[J]. Growth Factors, 2019, 37(3-4):105-119.
34
Huang B, Cheng X, Wang H, et al. Mesenchymal stem cells and their secreted molecules predominantly ameliorate fulminant hepatic failure and chronic liver fibrosis in mice respectively[J]. J Transl Med, 2016, 14:45.
35
Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation[J]. Mol Ther, 2012, 20(1):14-20.
36
Bassi EJ, de Almeida DC, Moraes-Vieira PM, et al. Exploring the role of soluble factors associated with immune regulatory properties of mesenchymal stem cells[J]. Stem Cell Rev Rep, 2012, 8(2):329-342.
37
Bian L, Guo ZK, Wang HX, et al. In vitro and in vivo immunosuppressive characteristics of hepatocyte growth factor-modified murine mesenchymal stem cells[J]. In Vivo, 2009, 23(1):21-27.
38
朱金海, 陈燕凌. 人肝细胞生长因子修饰的BMSCs对大鼠同种异体肝移植免疫排斥的影响[J]. 中国修复重建外科杂志, 2011, 25(7):871-876.
39
刘滋康, 具星爱, 靳继德, 等. 肝细胞生长因子基因修饰的人骨髓间充质干细胞促进大鼠肢体血管新生[J]. 组织工程与重建外科杂志, 2010, 6(2):61-65.
40
Su GH, Sun YF, Lu YX, et al. Hepatocyte growth factor gene-modified bone marrow-derived mesenchymal stem cells transplantation promotes angiogenesis in a rat model of hindlimb ischemia[J]. J Huazhong Univ Sci Technolog Med Sci, 2013, 33(4):511-519.
41
陈安平, 曾志勇, 刘洪涛, 等. 过表达HGF促慢性缺血心肌处血管生成的实验研究[J]. 中国现代医学杂志, 2012, 22(15):25-30.
42
Friedman SL. Mechanisms of hepatic fibrogenesis[J]. Gastroenterology, 2008, 134(6):1655-1669.
43
张君红. 肝细胞生长因子促进肝星状细胞凋亡的机制研究[D]. 南宁:广西医科大学, 2012.
44
Popov Y, Schuppan D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies[J]. Hepatology, 2009, 50(4):1294-1306.
45
Atta H, El-Rehany M, Hammam O, et al. Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression[J]. PLoS One, 2014, 9(11):e112384.
46
Zhang Y, Li R, Rong W, et al. Therapeutic effect of hepatocyte growth factor-overexpressing bone marrow-derived mesenchymal stem cells on CCl4-induced hepatocirrhosis[J]. Cell Death Dis, 2018, 9(12):1186.
47
Kim WH, Matsumoto K, Bessho K, et al. Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis[J]. Am J Pathol, 2005, 166(4):1017-1028.
48
苏思标, 姜海行, 王东旭, 等. 骨髓间充质干细胞调控肝星状细胞RhoA、P27的表达[J]. 世界华人消化杂志, 2009, 17(32):3283-3291.
49
陈国忠, 姜海行, 陆正峰, 等. 骨髓间充质干细胞共培养对肝星状细胞增殖、凋亡和RohA表达的调控[J]. 世界华人消化杂志, 2010, 18(16):1643-1649.
50
金银鹏. 间充质干细胞在肝脏疾病治疗中的历史性回顾及发展[J]. 肝脏, 2018, 23(3):193-196.
51
Yu Y, Lu L, Qian X, et al. Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats[J]. Stem Cells Dev, 2010, 19(6):903-914.
52
Pulavendran S, Rose C, Mandal AB. Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice[J]. J Nanobiotechnology, 2011, 9:15.
53
Deuse T, Peter C, Fedak PW, et al. Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction[J]. Circulation, 2009, 120(11 Suppl):S247-254.
54
陈瑶瑶, 李艳琪, 刘杨, 等. 肝细胞生长因子基因修饰的人脐带间充质干细胞对大鼠慢性肝损伤的治疗研究[J]. 生物技术通讯, 2013, 24(6): 767-772.
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