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间充质干细胞治疗肝脏疾病的急性不良反应与长期安全性

牛斌 吕傲 张缭云

引用本文:
Citation:

间充质干细胞治疗肝脏疾病的急性不良反应与长期安全性

DOI: 10.12449/JCH260530
基金项目: 

山西省重点研发计划 (201903D421056)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:牛斌负责论文框架,起草论文;吕傲负责文献查找,资料分析;张缭云负责拟定写作思路,指导撰写文章,修改论文并最后定稿。
详细信息
    通信作者:

    张缭云, zlysgzy@163.com (ORCID: 0000-0002-7666-7368)

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

Research funding: 

Shanxi Province Key Research and Development Program (201903D421056)

More Information
    Corresponding author: ZHANG Liaoyun, zlysgzy@163.com (ORCID: 0000-0002-7666-7368)
  • 摘要: 间充质干细胞(MSC)因其多向分化潜能与免疫调节特性,近年来被广泛探讨用于肝脏疾病的治疗。现有证据显示,MSC在肝硬化、肝衰竭等终末期肝病中能够改善肝功能、减轻纤维化并促进肝细胞再生。然而,随着临床应用的推进,其安全性问题也日益受到关注。本文系统综述了MSC治疗肝脏疾病时的急性不良反应与长期安全性。研究显示,MSC治疗总体安全性良好,急性不良反应以发热、皮疹及轻度过敏最为常见,多为自限性或经对症处理后可缓解;长期随访未见肿瘤发生风险显著升高,但部分研究提示MSC与肝细胞癌发生存在潜在关联。此外,栓塞形成、免疫排斥及感染易感性升高仍是需持续监测的风险。总体而言,MSC治疗肝脏疾病在近期疗效与安全性方面展现出良好前景,但仍需通过大样本、长期随访的临床研究以进一步验证其长期安全性与有效性。

     

  • [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.
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  • 收稿日期:  2025-08-08
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