中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 42 Issue 5
May  2026
Turn off MathJax
Article Contents

Acute adverse reactions and long-term safety of mesenchymal stem cells in treatment of liver diseases

DOI: 10.12449/JCH260530
Research funding:

Shanxi Province Key Research and Development Program (201903D421056)

More Information
  • Corresponding author: ZHANG Liaoyun, zlysgzy@163.com (ORCID: 0000-0002-7666-7368)
  • Received Date: 2025-08-08
  • Accepted Date: 2025-11-04
  • Published Date: 2026-05-25
  • In recent years, mesenchymal stem cells (MSC) have been widely explored in the treatment of liver diseases due to their characteristics of multipotential differentiation and immunomodulatory capabilities. Current evidence has shown that MSC therapy can improve liver function, alleviate fibrosis, and promote hepatocyte regeneration in end-stage liver diseases such as liver cirrhosis and liver failure. However, safety concerns have emerged with the increasing clinical use of MSC. This article systematically reviews the acute adverse reactions and long-term safety of MSC-based therapies for liver diseases. It is shown that MSC therapy has a good overall safety profile, with common acute adverse reactions of fever, rash, and mild allergy, most of which are self-limiting or can be alleviated by symptomatic treatment. No clear evidence of tumorigenesis has been reported in long-term follow-up, but some studies have suggested a potential association between MSC and the development of hepatocellular carcinoma. In addition, the risks of embolism, immune rejection, and infection susceptibility should be monitored continuously. Overall, MSC therapy shows good prospects in short-term efficacy and safety in the treatment of liver diseases, but clinical studies with a large sample size and a long follow-up period are needed to further validate its long-term safety and efficacy.

     

  • loading
  • [1]
    CHEN XW, DING GJ, XU L, et al. A glimpse at the metabolic research in China[J]. Cell Metab, 2021, 33( 11): 2122- 2125. DOI: 10.1016/j.cmet.2021.09.014.
    [2]
    WU MY, QIN SX, TAN CQ, et al. Estimated projection of incidence and mortality of alcohol-related liver disease in China from 2022 to 2040: A modeling study[J]. BMC Med, 2023, 21( 1): 277. DOI: 10.1186/s12916-023-02984-7.
    [3]
    FENG Y, CHEN JF, LIN BL. Clinical research advances in mesenchymal stem cells for the treatment of end-stage liver disease[J]. J Clin Hepatol, 2023, 39( 5): 1010- 1018. DOI: 10.3969/j.issn.1001-5256.2023.05.003.

    冯宇, 陈俊峰, 林炳亮. 间充质干细胞治疗终末期肝病的临床研究进展[J]. 临床肝胆病杂志, 2023, 39( 5): 1010- 1018. DOI: 10.3969/j.issn.1001-5256.2023.05.003.
    [4]
    YANG L, FENG BS. Research progress of extracellular vesicles derived from mesenchymal stem cells in liver diseases[J]. Chin J Hepatol, 2023, 31( 5): 556- 560. DOI: 10.3760/cma.j.cn501113-20230320-00123.

    杨柳, 冯百岁. 间充质干细胞源性细胞外囊泡在肝脏疾病中的研究进展[J]. 中华肝脏病杂志, 2023, 31( 5): 556- 560. DOI: 10.3760/cma.j.cn501113-20230320-00123.
    [5]
    HU XH, CHEN L, WU H, et al. Cell therapy in end-stage liver disease: Replace and remodel[J]. Stem Cell Res Ther, 2023, 14( 1): 141. DOI: 10.1186/s13287-023-03370-z.
    [6]
    ClinicalTrials. gov. Search results for“Liver, MSC”[EB/OL].[ 2025-05-16]. https://clinicaltrials.gov/search?cond=Liver&intr=MSC&viewType=Table. https://clinicaltrials.gov/search?cond=Liver&intr=MSC&viewType=Table
    [7]
    HAN Y, GUO CC, SHI YQ. Expert consensus on standardized treatment of decompensated liver cirrhosis with stem cell transplantation(2021)[J]. J Clin Hepatol, 2021, 37( 7): 1540- 1544. DOI: 10.3969/j.issn.1001-5256.2021.07.012

    韩英, 郭长存, 时永全. 干细胞移植规范化治疗肝硬化失代偿的专家共识(2021)[J]. 临床肝胆病杂志, 2021, 37( 7): 1540- 1544. DOI: 10.3969/j.issn.1001-5256.2021.07.012.
    [8]
    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.
    [9]
    THOMPSON M, MEI SHJ, WOLFE D, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis[J]. EClinicalMedicine, 2020, 19: 100249. DOI: 10.1016/j.eclinm.2019.100249.
    [10]
    WANG Y, MOU QY, YI HX, et al. Transient fever: The sole treatment-related adverse event associatedwith mesenchymal stromal cells and solid clues from the real world[J]. Curr Stem Cell Res Ther, 2024, 19( 9): 1263- 1285. DOI: 10.2174/011574888x179799231023060734.
    [11]
    HENDRICKSON JE, HILLYER CD. Noninfectious serious hazards of transfusion[J]. Anesth Analg, 2009, 108( 3): 759- 769. DOI: 10.1213/ane.0b013e3181930a6e.
    [12]
    WANG Y, YI HX, SONG YC. The safety of MSC therapy over the past 15 years: A meta-analysis[J]. Stem Cell Res Ther, 2021, 12( 1): 545. DOI: 10.1186/s13287-021-02609-x.
    [13]
    KOT M, BAJ-KRZYWORZEKA M, SZATANEK R, et al. The importance of HLA assessment in“off-the-shelf” allogeneic mesenchymal stem cells based-therapies[J]. Int J Mol Sci, 2019, 20( 22): 5680. DOI: 10.3390/ijms20225680.
    [14]
    SHAHDADFAR A, FRØNSDAL K, HAUG T, et al. In vitro expansion of human mesenchymal stem cells: Choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability[J]. Stem Cells, 2005, 23( 9): 1357- 1366. DOI: 10.1634/stemcells.2005-0094.
    [15]
    LALU MM, MCINTYRE L, PUGLIESE C, et al. Safety of cell therapy with mesenchymal stromal cells(SafeCell): A systematic review and meta-analysis of clinical trials[J]. PLoS One, 2012, 7( 10): e47559. DOI: 10.1371/journal.pone.0047559.
    [16]
    VALENTINI CG, PELLEGRINO C, TEOFILI L. Pros and cons of cryopreserving allogeneic stem cell products[J]. Cells, 2024, 13( 6): 552. DOI: 10.3390/cells13060552.
    [17]
    HEE K, YOUNG K, WOO E, et al. Mesenchymal stem cells for the treatment of liver disease: Present and perspectives[J]. Gut Liver, 2020, 14( 3): 306- 315. DOI: 10.5009/gnl18412.
    [18]
    MOJSILOVIĆ S, JAUKOVIĆ A, KUKOLJ T, et al. Tumorigenic aspects of MSC senescence-implication in cancer development and therapy[J]. J Pers Med, 2021, 11( 11): 1133. DOI: 10.3390/jpm11111133.
    [19]
    METWALLY AM, LI HC, HOUGHTON J. Alterations of epigenetic regulators and P53 mutations in murine mesenchymal stem cell cultures: A possible mechanism of spontaneous transformation[J]. Cancer Biomark, 2021, 32( 3): 327- 337. DOI: 10.3233/CBM-203121.
    [20]
    CASIRAGHI F, REMUZZI G, ABBATE M, et al. Multipotent mesenchymal stromal cell therapy and risk of malignancies[J]. Stem Cell Rev Rep, 2013, 9( 1): 65- 79. DOI: 10.1007/s12015-011-9345-4.
    [21]
    STIRPARO GG, SMITH A, GUO G. Cancer-related mutations are not enriched in naive human pluripotent stem cells[J]. Cell Stem Cell, 2021, 28( 1): 164- 169. e 2. DOI: 10.1016/j.stem.2020.11.014.
    [22]
    SIRAJ Y, GALDERISI U, ALESSIO N. Senescence induces fundamental changes in the secretome of mesenchymal stromal cells(MSCs): Implications for the therapeutic use of MSCs and their derivates[J]. Front Bioeng Biotechnol, 2023, 11: 1148761. DOI: 10.3389/fbioe.2023.1148761.
    [23]
    BANIMOHAMAD-SHOTORBANI B, KAHROBA H, SADEGHZADEH H, et al. DNA damage repair response in mesenchymal stromal cells: From cellular senescence and aging to apoptosis and differentiation ability[J]. Ageing Res Rev, 2020, 62: 101125. DOI: 10.1016/j.arr.2020.101125.
    [24]
    DI GH, LIU Y, LU Y, et al. IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells[J]. PLoS One, 2014, 9( 11): e113572. DOI: 10.1371/journal.pone.0113572.
    [25]
    AL-AZAB M, SAFI M, IDIIATULLINA E, et al. Aging of mesenchymal stem cell: Machinery, markers, and strategies of fighting[J]. Cell Mol Biol Lett, 2022, 27( 1): 69. DOI: 10.1186/s11658-022-00366-0.
    [26]
    GHOLAMREZANEZHAD A, MIRPOUR S, BAGHERI M, et al. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis[J]. Nucl Med Biol, 2011, 38( 7): 961- 967. DOI: 10.1016/j.nucmedbio.2011.03.008.
    [27]
    THANASKODY K, JUSOP AS, TYE GJ, et al. MSCs vs. iPSCs: Potential in therapeutic applications[J]. Front Cell Dev Biol, 2022, 10: 1005926. DOI: 10.3389/fcell.2022.1005926.
    [28]
    PONCELET AJ, VERCRUYSSE J, SALIEZ A, et al. Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo[J]. Transplantation, 2007, 83( 6): 783- 790. DOI: 10.1097/01.tp.0000258649.23081.a3.
    [29]
    WANG YF, HUANG JY, GONG L, et al. The plasticity of mesenchymal stem cells in regulating surface HLA-I[J]. iScience, 2019, 15: 66- 78. DOI: 10.1016/j.isci.2019.04.011.
    [30]
    ZHOU T, YUAN ZN, WENG JY, et al. Challenges and advances in clinical applications of mesenchymal stromal cells[J]. J Hematol Oncol, 2021, 14( 1): 24. DOI: 10.1186/s13045-021-01037-x.
    [31]
    YUDINTCEVA N, MIKHAILOVA N, FEDOROV V, et al. Mesenchymal stem cells and MSCs-derived extracellular vesicles in infectious diseases: From basic research to clinical practice[J]. Bioengineering, 2022, 9( 11): 662. DOI: 10.3390/bioengineering9110662.
    [32]
    XU WX, HE HL, PAN SW, et al. Combination treatments of plasma exchange and umbilical cord-derived mesenchymal stem cell transplantation for patients with hepatitis B virus-related acute-on-chronic liver failure: A clinical trial in China[J]. Stem Cells Int, 2019, 2019: 4130757. DOI: 10.1155/2019/4130757.
    [33]
    WANG LF, LI J, LIU HH, et al. Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis[J]. J Gastroenterol Hepatol, 2013, 28( Suppl 1): 85- 92. DOI: 10.1111/jgh.12029.
    [34]
    SHI L, ZHANG ZY, MEI S, et al. Dose-escalation studies of mesenchymal stromal cell therapy for decompensated liver cirrhosis: Phase Ia/Ib results and immune modulation insights[J]. Signal Transduct Target Ther, 2025, 10( 1): 238. DOI: 10.1038/s41392-025-02318-4.
    [35]
    LIN BL, CHEN JF, QIU WH, et al. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial[J]. Hepatology, 2017, 66( 1): 209- 219. DOI: 10.1002/hep.29189.
    [36]
    FANG XQ, LIU LW, DONG J, et al. A study about immunomodulatory effect and efficacy and prognosis of human umbilical cord mesenchymal stem cells in patients with chronic hepatitis B-induced decompensated liver cirrhosis[J]. J Gastroenterol Hepatol, 2018, 33( 4): 774- 780. DOI: 10.1111/jgh.14081.
    [37]
    TAE S, YOON JH, YOUNG K, et al. Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial[J]. Hepatology, 2016, 64( 6): 2185- 2197. DOI: 10.1002/hep.28693.
    [38]
    LI ZP, ZHOU XL, HAN L, et al. Human umbilical cord blood-derived mesenchymal stem cell transplantation for patients with decompensated liver cirrhosis[J]. J Gastrointest Surg, 2023, 27( 5): 926- 931. DOI: 10.1007/s11605-022-05528-1.
    [39]
    LI YH, XU Y, WU HM, et al. Umbilical cord-derived mesenchymal stem cell transplantation in hepatitis B virus related acute-on-chronic liver failure treated with plasma exchange and entecavir: A 24-month prospective study[J]. Stem Cell Rev Rep, 2016, 12( 6): 645- 653. DOI: 10.1007/s12015-016-9683-3.
    [40]
    SHI M, LI YY, XU RN, et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis: A long-term follow-up analysis of the randomized controlled clinical trial[J]. Hepatol Int, 2021, 15( 6): 1431- 1441. DOI: 10.1007/s12072-021-10199-2.
    [41]
    PENG L, XIE DY, LIN BL, et al. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short-term and long-term outcomes[J]. Hepatology, 2011, 54( 3): 820- 828. DOI: 10.1002/hep.24434.
    [42]
    WANG MF, LI YB, GAO XJ, et al. Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study[J]. World J Stem Cells, 2018, 10( 10): 138- 145. DOI: 10.4252/wjsc.v10.i10.138.
    [43]
    di BONZO LV, FERRERO I, CRAVANZOLA C, et al. Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: Engraftment and hepatocyte differentiation versus profibrogenic potential[J]. Gut, 2008, 57( 2): 223- 231. DOI: 10.1136/gut.2006.111617.
    [44]
    LU WM, QU JY, YAN LX, et al. Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: A systematic review and meta-analysis[J]. Stem Cell Res Ther, 2023, 14( 1): 301. DOI: 10.1186/s13287-023-03518-x.
    [45]
    TOYSERKANI NM, JØRGENSEN MG, TABATABAEIFAR S, et al. Concise review: A safety assessment of adipose-derived cell therapy in clinical trials: A systematic review of reported adverse events[J]. Stem Cells Transl Med, 2017, 6( 9): 1786- 1794. DOI: 10.1002/sctm.17-0031.
    [46]
    The Rheumatology Branch of the Chinese Medical Association, the Professional Committee for Clinical Application of New Technologies of the China Hospital Association. Expert consensus on allogeneic mesenchymal stem cells in the treatment of systemic lupus erythematosus[J]. Chin J Rheumatol, 2022, 26( 1): 1- 8. DOI: 10.3760/cma.j.cn141217-20210923-00381.

    中华医学会风湿病学分会, 中国医院协会临床新技术应用专业委员会. 异体间充质干细胞治疗系统性红斑狼疮专家共识[J]. 中华风湿病学杂志, 2022, 26( 1): 1- 8. DOI: 10.3760/cma.j.cn141217-20210923-00381.
    [47]
    National Health Commission of the People’s Republic of China, Medical Administration and Hospital Authority. Standard for Diagnosis and Treatment of Primary Liver Cancer(2019 Edition)[J]. J Clin Hepatol, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.

    中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.
  • 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

    Article Metrics

    Article views (33) PDF downloads(10) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return