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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 8
Aug.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(8): 1822-1828

Effect of combined treatment with human umbilical cord blood mononuclear cells and human umbilical cord mesenchymal stem cells on liver function, inflammation grade, and immune function in patients with hepatitis B cirrhosis

DOI: 10.3969/j.issn.1001-5256.2021.08.016

  • Stem Cell Laboratory, Affiliated Hospital of Inner Mongolia Medical University, Stem Cell Center of Inner Mongolia Medical University, Hohhot 010050, China

Research funding:

Inner Mongolia Medical University Science and Technology One Million Engineering Joint Joint Venture Project (YKD2017KJBW〔LH〕05);

Inner Mongolia Autonomous Region Science and Technology Department Funded Project (201802150)

  • Received Date: 2020-12-01
  • Accepted Date: 2021-02-23
  • Published Date: 2021-08-20
    Abstract
  •   Objective  To retrospectively investigate the effect of combined treatment with human umbilical cord blood mononuclear cells (hUCB-MNCs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) on liver function, inflammation grade, and immune function in patients with hepatitis B-related decompensated cirrhosis.  Methods  11 patients with liver cirrhosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from November 2016 to June 2019 were enrolled in this clinical study and were given infusion of hUCB-MNCs (> 18×109/time) once in the first week and infusion of hUC-MSCs (1×106/kg) once a week in the second, third, and fourth weeks. Reexamination was performed at 4, 8, and 12 weeks after treatment to compare the changes in liver function, blood ammonia, blood coagulation factors, serum levels of cytokines, and lymphocyte subsets after treatment, and the changes in neurological and psychiatric symptoms were observed and recorded. A one-way repeated-measures analysis of variance was used for comparison of continuous data between groups.  Results  After the combined treatment with hUCB-MNCs and hUC-MSCs, all 11 patients achieved certain improvements in psychiatric and neurological symptoms after infusion, and liver function parameters and blood coagulation function basically returned to normal (all P < 0.05). At 12 weeks after the combined infusion of cells, blood ammonia level returned to the normal level (P < 0.05), and there were significant reductions in the levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor (F=49.497 and 37.071, both P < 0.05) and significant increases in the levels of the anti-inflammatory cytokines transforming growth factor-β and interleukin-10 (F=35.843 and 15.918, both P < 0.05). There were also significant reductions in the percentages of the cytotoxic cells CD3+CD8+ T and CD19+ B cells (F=52.242 and 89.097, both P < 0.05) and a significant increase in the regulatory T cells CD4+CD25+ (F=17.337, P < 0.05).  Conclusion  Combined treatment with hUCB-MNCs and hUC-MSCs for liver cirrhosis can optimize liver function, reduce the production of inflammatory cytokines, alleviate liver inflammation and liver cell destruction, and increase regulatory T cells, thereby affecting the body's immune function.

     

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    • References(26)
  • [1]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
    [2]
    HOWS J, NICOL A, DENNING-KENDALL P, et al. Cord blood as an alternative source of haemopoietic stem cells[J]. Ann Oncol, 1996, 7(Suppl 2): 47-51. DOI: 10.1093/annonc/7.suppl_2.47.
    [3]
    TAO H, LI Y, WANG T, et al. Umbilical cord blood stem cells transplantation as an adjunctive treatment strategy for liver cirrhosis in Chinese population: A meta-analysis of effectiveness and safety[J]. Ther Clin Risk Manag, 2018, 14: 417-440. DOI: 10.2147/TCRM.S157603.
    [4]
    ZHAO L, CHEN S, SHI X, et al. A pooled analysis of mesenchymal stem cell-based therapy for liver disease[J]. Stem Cell Res Ther, 2018, 9(1): 72. DOI: 10.1186/s13287-018-0816-2.
    [5]
    VANGSNESS CT Jr, STERNBERG H, HARRIS L. Umbilical cord tissue offers the greatest number of harvestable mesenchymal stem cells for and clinical application: A literature review of different harvest sites[J]. Arthroscopy, 2015, 31(9): 1836-1843. DOI: 10.1016/j.arthro.2015.03.014.
    [6]
    QIU Y, ZHAO R, YUN MM, et al. Immunity enhancement in immunocompromised gastrointestinal cancer patients with allogeneic umbilical cord blood mononuclear cell transfusion[J]. Biomed Res Int, 2017, 2017: 5945190. DOI: 10.1155/2017/5945190.
    [7]
    KIM G, EOM YW, BAIK SK, et al. Therapeutic effects of mesenchymal stem cells for patients with chronic liver diseases: Systematic review and meta-analysis[J]. J Korean Med Sci, 2015, 30(10): 1405-1415. DOI: 10.3346/jkms.2015.30.10.1405.
    [8]
    LIU AX, WANG W, ZHONG ZB, et al. progress on the immunomodulatory effects of mesenchymal stem cells in the treatment of end-stage liver disease[J/CD]. Chin J Transplant(Electronic Edition), 2020, 14(1): 49-53. DOI: 10.3877/cma.j.issn.1674-3903.2020.01.013.

    柳安雄, 王伟, 钟自彪, 等. 间充质干细胞免疫调节作用在终末期肝病治疗中的研究进展[J/CD]. 中华移植杂志(电子版), 2020, 14(1): 49-53. DOI: 10.3877/cma.j.issn.1674-3903.2020.01.013.
    [9]
    YU YB, GU DH. Comparison of differentiation of human umbilical cord mesenchymal stem cells and bone marrow mesenchymal stem cells into hepatocytes[J]. Chin J Hepatobiliary Surg, 2016, 22(1): 13-16. DOI: 10.3760/cma.j.issn.1007-8118.2016.01.005.

    禹亚彬, 顾殿华. 人脐带间充质干细胞与骨髓间充质干细胞向肝细胞分化的比较[J]. 中华肝胆外科杂志, 2016, 22(1): 13-16. DOI: 10.3760/cma.j.issn.1007-8118.2016.01.005.
    [10]
    WANG L, HAN Q, CHEN H, et al. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis[J]. Stem Cells Dev, 2014, 23(20): 2482-2489. DOI: 10.1089/scd.2013.0500.
    [11]
    LUIS AS, XÓCHITL GS, SUSANA AL, et al. Levels of TNF-α, IL-1β, TGF-β, and IL-6 in patients with chronic hepatitis C virus infection and hyperinsulinemia[J]. Open J Immunol, 2013, 3(1): 17-23. DOI: 10.4236/oji.2013.31003.
    [12]
    ZHANG JM, WANG W, YAO XM, et al. Clinical significance of combined detection of changes of serum AFP, TNF-α, IL-6, IL-10 levels in patients with liver cirrhosis[J]. J Radioimmunol, 2007, 20(3): 221-223. DOI: 10.3969/j.issn.1008-9810.2007.03.015.

    张家明, 王文, 姚孝明, 等. 肝硬化患者血清AFP、TNF-α、IL-6、IL-10检测的临床意义[J]. 放射免疫学杂志, 2007, 20(3): 221-223. DOI: 10.3969/j.issn.1008-9810.2007.03.015.
    [13]
    Chinese Society of Infectious Diseases and Parasitology, Chinese Society of Hepatology, Chinese Medical Association. Prevention and treatment of viral hepatitis[J]. Chin J Infect Dis, 2001, 19(1): 56-62. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHCR200101022.htm

    中华医学会传染病与寄生虫病学分会、肝病学分会. 病毒性肝炎防治方案[J]. 中华传染病杂志, 2001, 19(1): 56-62. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHCR200101022.htm
    [14]
    YAO GB. Development and progress——Interpretation of "Guidelines for Prevention and Treatment of Chronic Hepatitis B in 2005"[J]. Liver, 2006, 11(4): 225-226. DOI: 10.14000/j.cnki.issn.1008-1704.2006.04.001.

    姚光弼. 发展与进步——解读《2005年慢性乙型肝炎防治指南》[J]. 肝脏, 2006, 11(4): 225-226. DOI: 10.14000/j.cnki.issn.1008-1704.2006.04.001.
    [15]
    KLIONSKY DJ, ABDELMOHSEN K, ABE A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)[J]. Autophagy, 2016, 12(1): 1-222. DOI: 10.1080/15548627.2015.1100356.
    [16]
    LI C, DUAN SQ, YAN SH. Analysis of the epidemiological characteristics of viral hepatitis B in Inner Mongolia Autonomous Region from 1991 to 2010[J]. Dis Surveill, 2012, 27(1): 20-24. DOI: 10.3784/j.issn.1003-9961.2012.1.008.

    李澄, 段术琴, 闫绍宏. 1991-2010年内蒙古自治区乙型病毒性肝炎流行病学特征分析[J]. 疾病监测, 2012, 27(1): 20-24. DOI: 10.3784/j.issn.1003-9961.2012.1.008.
    [17]
    YAN JQ, HAN T, ZHU ZY. The biological characteristics of human umbilical cord mesenchymal stem cells and their differentiation into hepato-like cells[J]. World Chin J Dig, 2008, 16(15): 1639-1644. DOI: 10.3969/j.issn.1009-3079.2008.15.009.

    闫俊卿, 韩涛, 朱争艳. 人脐带间充质干细胞生物学特性及向类肝细胞的分化[J]. 世界华人消化杂志, 2008, 16(15): 1639-1644. DOI: 10.3969/j.issn.1009-3079.2008.15.009.
    [18]
    SHAN YB, FAN YW, SHI HC, et al. progress of mesenchymal stem cells in tissue engineering trachea[J]. Int J Biomed Eng, 2017, 40(3): 211-215. DOI: 10.3760/cma.j.issn.1673-4181.2017.03.014.

    单一波, 范懿魏, 史宏灿, 等. 间充质干细胞在组织工程气管中的研究进展[J]. 国际生物医学工程杂志, 2017, 40(3): 211-215. DOI: 10.3760/cma.j.issn.1673-4181.2017.03.014.
    [19]
    WAKAO S, MATSUSE D, DEZAWA M. Mesenchymal stem cells as a source of Schwann cells: Their anticipated use in peripheral nerve regeneration[J]. Cells Tissues Organs, 2014, 200(1): 31-41. DOI: 10.1159/000368188.
    [20]
    BOROUJENI ME, GARDANEH M. Umbilical cord: An unlimited source of cells differentiable towards dopaminergic neurons[J]. Neural Regen Res, 2017, 12(7): 1186-1192. DOI: 10.4103/1673-5374.211201.
    [21]
    ZHAN GQ, ZHENG SJ, ZHU L, et al. The analysis of prognosis of patients with decompensated liver cirrhosis using the criterion of the model for end-stage liver disease and Child-Pugh grading[J]. J Clin Hepatol, 2009, 25(2): 114-116. http://lcgdbzz.org/article/id/LCGD200902012

    占国清, 郑三菊, 朱琳, 等. 终末期肝病模型及Child-Pugh分级对失代偿期肝硬化患者的预后分析[J]. 临床肝胆病杂志, 2009, 25(2): 114-116. http://lcgdbzz.org/article/id/LCGD200902012
    [22]
    LIU MW, LIU MY, HU X, et al. Study on the immunoregulatory function of exosomes of human umbilical cord mesenchymal stem cells[J]. Natl Med J China, 2015, 95(32): 2630-2633. DOI: 10.3760/cma.j.issn.0376-2491.2015.32.014.

    刘明汪, 刘沐芸, 胡祥, 等. 人脐带间充质干细胞外泌体免疫调节功能的研究[J]. 中华医学杂志, 2015, 95(32): 2630-2633. DOI: 10.3760/cma.j.issn.0376-2491.2015.32.014.
    [23]
    WANG Y, CHEN LJ. progress on the immune regulation function of umbilical cord mesenchymal stem cells[J]. Chin J Cell Mol Immunol, 2017, 33(7): 1001-1006. DOI: 10.13423/j.cnki.cjcmi.008206.

    王雨, 陈龙菊. 脐带间充质干细胞免疫调节功能的研究进展[J]. 细胞与分子免疫学杂志, 2017, 33(7): 1001-1006. DOI: 10.13423/j.cnki.cjcmi.008206.
    [24]
    WEI XH, LIU YL, ZHANG J, et al. Expression and clinical significance of serum cytokines in children with acute hepatitis A[J]. J Clin Hepatol, 2019, 35(9): 1942-1945. DOI: 10.3969/j.issn.1001-5256.2019.09.011.

    韦新焕, 柳雅立, 张晶, 等. 血清细胞因子在急性甲型肝炎患儿中的表达及临床意义[J]. 临床肝胆病杂志, 2019, 35(9): 1942-1945. DOI: 10.3969/j.issn.1001-5256.2019.09.011.
    [25]
    ZHOU L, LOPES JE, CHONG MM, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function[J]. Nature, 2008, 453(7192): 236-240. DOI: 10.1038/nature06878.
    [26]
    de MIGUEL MP, FUENTES-JULIÁN S, BLÁZQUEZ-MARTÍNEZ A, et al. Immunosuppressive properties of mesenchymal stem cells: Advances and applications[J]. Curr Mol Med, 2012, 12(5): 574-591. DOI: 10.2174/156652412800619950.
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