中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 6
Jun.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(6): 1209-1214

Effect of mesenchymal stem cells combined with immunosuppressants on immune rejection in a rat model of liver transplantation

DOI: 10.12449/JCH240622
  • 1a.

    Department of Minimally Invasive Hepatopancreatobiliary Surgery,Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350011, China

  • 1b.

    Department of Pathology，Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350011, China

  • 2.

    College of Biological Science and Engineering, Fuzhou University，Fuzhou 350016，China

Research funding:

The Natural Science Foundation of Fujian Province (2020J011163);

The Medical Innovation Project of Fujian Province (2020CXA054);

Key Clinical Specialty Discipline Construction Program of Fuzhou (20230101)

More Information
  • Corresponding author: LI Haitao， lht45182@163.com （ORCID： 0000-0003-4680-4752）
  • Received Date: 2023-10-10
  • Accepted Date: 2023-11-08
  • Published Date: 2024-06-25
    Abstract
  •   Objective  To investigate the effect of mesenchymal stem cells （MSCs） combined with immunosuppressants （IS） on immune rejection in a rat model of liver transplantation.  Methods  F344 rats were divided into Normal group （without any intervention）， PS group （injected with an equal volume of normal saline）， MSC group （injected with MSC）， IS group （injected with IS）， and MSC+IS group （injected with MSC and IS）， with 8 rats in each group. For all rats except those in the Normal group， the Kamada’s double-cuff method was used to establish a model of orthotopic liver transplantation， without reconstruction of the hepatic artery. HE staining and Masson staining were performed for rat liver tissue， and the degree of liver fibrosis was analyzed； immunohistochemical experiments were used to measure the infiltration of T cells and NK cells， and immunofluorescence assay was used to analyze macrophage M2 polarization. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kaplan-Meier method was used to plot survival curves， and the log-rank test was used for survival analysis.  Results  Compared with the PS group， the MSC+IS group had a significantly prolonged survival time （P<0.01）， and the MSC group， the IS group， and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis （all P<0.000 1）， as well as a significant reduction in the infiltration of NK and T cells （all P<0.000 1） and a significant increase in the degree of macrophage M2 polarization （all P<0.000 1）. The MSC+IS group had a significantly better effect than the MSC group and the IS group.  Conclusion  MSCs combined with IS can improve liver histopathology， reduce inflammatory cell infiltration， promote macrophage M2 polarization， and exert an immunosuppressive effect in rats after liver transplantation.

     

    • FullText(HTML)
  • loading
    • References(16)
  • [1]
    NEUBERGER J. Developments in liver transplantation[J]. Gut, 2004, 53( 5): 759- 768. DOI: 10.1136/gut.2003.024927.
    [2]
    HONG SK, HAN D, LEE SK, et al. Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman Primates[J]. Am J Transplant, 2021, 21( 9): 2978- 2991. DOI: 10.1111/ajt.16486.
    [3]
    Branch of Organ Tansplantation of Chinese Medical Association. Diagnosis and treatment specification for immunosuppressive therapy and rejection of liver transplantation in China(2019 edition)[J]. Organ Transplant, 2021, 12( 1): 8- 14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002.

    中华医学会器官移植学分会. 中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)[J]. 器官移植, 2021, 12( 1): 8- 14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002.
    [4]
    TAN PS, MUTHIAH MD, KOH T, et al. Asian liver transplant network clinical guidelines on immunosuppression in liver transplantation[J]. Transplantation, 2019, 103( 3): 470- 480. DOI: 10.1097/TP.0000000000002532.
    [5]
    DI MAIRA T, LITTLE EC, BERENGUER M. Immunosuppression in liver transplant[J]. Best Pract Res Clin Gastroenterol, 2020, 46-47: 101681. DOI: 10.1016/j.bpg.2020.101681.
    [6]
    ZHAO L, CHEN SQ, SHI XW, 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.
    [7]
    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. DOI: 10.1080/14653240600855905.
    [8]
    LU XF, GUO HJ, WEI XY, et al. Current status and prospect of delivery vehicle based on mesenchymal stem cell-derived exosomes in liver diseases[J]. Int J Nanomedicine, 2023, 18: 2873- 2890. DOI: 10.2147/IJN.S404925.
    [9]
    LI HT, YU SH, CHEN LH, et al. Immunomodulatory role of mesenchymal stem cells in liver transplantation: Status and prospects[J]. Dig Dis Basel Switz, 2024, 42( 1): 41- 52. DOI: 10.1159/000534003.
    [10]
    KAMADA N, CALNE RY. Orthotopic liver transplantation in the rat[J]. Transplantation, 1979, 28( 1): 47- 50. DOI: 10.1097/00007890-197907000-00011.
    [11]
    CEN YL, LOU GH, QI JJ, et al. Adipose-derived mesenchymal stem cells inhibit JNK-mediated mitochondrial retrograde pathway to alleviate acetaminophen-induced liver injury[J]. Antioxidants, 2023, 12( 1): 158. DOI: 10.3390/antiox12010158.
    [12]
    ZHOU Q, RONG C, GU TF, et al. Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p-mediated inhibition of Notch signaling pathway[J]. Stem Cell Res Ther, 2022, 13( 1): 354. DOI: 10.1186/s13287-022-03030-8.
    [13]
    TIAN SY, ZHOU X, ZHANG M, et al. Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages[J]. Stem Cell Res Ther, 2022, 13( 1): 330. DOI: 10.1186/s13287-022-03010-y.
    [14]
    MONTANO-LOZA AJ, RODRÍGUEZ-PERÁLVAREZ ML, PAGEAUX GP, et al. Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation[J]. J Hepatol, 2023, 78( 6): 1199- 1215. DOI: 10.1016/j.jhep.2023.01.030.
    [15]
    D'ELIA JA, WEINRAUCH LA. Hyperglycemia and hyperlipidemia with kidney or liver transplantation: A review[J]. Biology, 2023, 12( 9): 1185. DOI: 10.3390/biology12091185.
    [16]
    NORÉN Å, OLTEAN M, FRIMAN S, et al. Liver graft proteomics reveals potential incipient mechanisms behind early renal dysfunction after liver transplantation[J]. Int J Mol Sci, 2022, 23( 19): 11929. DOI: 10.3390/ijms231911929.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(8)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (38) PDF downloads(10) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return