间充质干细胞治疗终末期肝病的研究进展及应用前景

张熠彤; 辛磊; 李兆申

doi:10.3969/j.issn.1001-5256.2019.09.049

间充质干细胞治疗终末期肝病的研究进展及应用前景

DOI: 10.3969/j.issn.1001-5256.2019.09.049

海军军医大学长海医院消化内科

基金项目:

国家科技重大专项子任务(2018ZX10302207-001-004)；

详细信息

中图分类号: R575.3
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- 被引次数: 0
出版历程
- 收稿日期: 2019-05-30
- 出版日期: 2019-09-20

Research advances in mesenchymal stem cells in treatment of end-stage liver disease and their application prospect

Department of Gastroenterology, Changhai Hospital, Naval Medical University

Research funding:

摘要

摘要: 终末期肝病是各种进行性肝病的终点,病死率高,严重危害人类健康。近期国内外研究显示间充质干细胞移植治疗终末期肝病安全有效。对目前国内外该领域的动物实验、临床试验及基础研究进行总结分析,探讨提高间充质干细胞疗效的可行方案和未来的临床应用前景。
- 终末期肝病 /
- 间质干细胞移植 /
- 治疗结果
Abstract: End-stage liver disease is the end point of various progressive liver diseases and has high mortality, which greatly threatens human health. Recent studies in China and foreign countries have shown that mesenchymal stem cell ( MSC) transplantation is a safe and effective treatment method for end-stage liver disease. This article summarizes the animal experiments, clinical trials, and basic research in this field and discusses the feasible strategies to enhance the clinical effect of MSCs and the application prospect of MSCs.
- end-stage liver disease /
- mesenchymal stem cell transplantation /
- treatment outcome

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参考文献(41)

[1] LEE CW, CHEN YF, WU HH, et al. Historical perspectives and advances in mesenchymal stem cell research for the treatment of liver diseases[J]. Gastroenterology, 2018, 154 (1) :46-56.

[2] WU DB, CHEN EQ, TANG H. Stem cell transplantation for the treatment of end-stage liver disease[J]. World J Hepatol, 2018, 10 (12) :907-910.

[3] TAO YC, WANG ML, CHEN EQ, et al. Stem cells transplantation in the treatment of patients with liver failure[J]. Curr Stem Cell Res Ther, 2018, 13 (3) :193-201.

[4] QU ZP, JIA ZF, HUANG X, et al. Research advances in the application of mesenchymal stem cells in organ transplantation[J]. Ogran Transplantation, 2018, 9 (5) :348-353. (in Chinese) 曲泽澎, 贾兆锋, 黄曦, 等.间充质干细胞在器官移植中的应用研究进展[J].器官移植, 2018, 9 (5) :348-353.

[5] XIAO XX, LIANG R. Research advances in stem cell transplantation for the treatment of acute-on-chronic liver failure[J]. J Clin Hepatol, 2017, 33 (8) :1576-1580. (in Chinese) 肖笑枭, 梁锐.干细胞移植治疗慢加急性肝衰竭的研究进展[J].临床肝胆病杂志, 2017, 33 (8) :1576-1580.

[6] TANIMOTO H, TERAI S, TARO T, et al. Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow[J]. Cell Tissue Res, 2013, 354 (3) :717-728.

[7] 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 (1) :45.

[8] CHAI NL, ZHANG XB, CHEN SW, et al. Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats[J].World J Gastroenterol, 2016, 22 (26) :6036-6048.

[9] YAMAZA T, ALATAS FS, YUNIARTHA R, et al. In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice[J].Stem Cell Res Ther, 2015, 6 (1) :171.

[10] YAMATO M, SAKAI Y, MOCHIDA H, et al. Adipose tissuederived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL-17-mediated inflammation[J]. J Gastroenterol Hepatol, 2019.[Epub ahead of print]

[11] SASSER AK, SULLIVAN NJ, STUDEBAKER AW, et al. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer[J]. Faseb J, 2007, 21 (13) :3763-3770.

[12] KARNOUB AE, DASH AB, VO AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis[J]. Nature, 2007, 449 (7162) :557-563.

[13] MATSUURA K, TAKAMI T, MAEDA M, et al. Evaluation of the effects of cultured bone marrow mesenchymal stem cell infusion on hepatocarcinogenesis in hepatocarcinogenic mice with liver cirrhosis[J]. Transplant Proc, 2019, 51 (3) :925-935.

[14] MOHAMADNEJAD M, ALIMOGHADDAM K, MOHYEDDINBONAB M, et al. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis[J]. Arch Iran Med, 2007, 10 (4) :459-466.

[15] KHARAZIHA P, HELLSTROM PM, NOORINAYER B, et al. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection:A phase I-II clinical trial[J]. Eur J Gastroenterol Hepatol, 2009, 21 (10) :1199-1205.

[16] SUK KT, YOON JH, KIM MY, et al. Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis:Phase 2 trial[J]. Hepatology, 2016, 64 (6) :2185-2197.

[17] LIN BL, CHEN JF, QIU WH, et al. Allogeneic bone marrowderived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure:A randomized controlled trial[J]. Hepatology, 2017, 66 (1) :209-219.

[18] MOHAMADNEJAD M, ALIMOGHADDAM K, BAGHERI M, et al. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis[J]. Liver Int, 2013, 33 (10) :1490-1496.

[19] WANG L, LI J, LIU H, 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.

[20] ZHANG Z, LIN H, SHI M, et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients[J]. J Gastroenterol Hepatol, 2012, 27 (Suppl 2) :112-120.

[21] KHAN AA, SHAIK MV, PARVEEN N, et al. Human fetal liverderived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis[J]. Cell Transplant, 2010, 19 (4) :409-418.

[22] AMER ME, EL-SAYED SZ, EL-KHEIR WA, et al. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells[J]. Eur J Gastroenterol Hepatol, 2011, 23 (10) :936-941.

[23] LEE KD, KUO TK, WHANG-PENG J, et al. In vitro hepatic differentiation of human mesenchymal stem cells[J]. Hepatology, 2004, 40 (6) :1275-1284.

[24] DI NICOLA M, CARLO-STELLA C, MAGNI M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli[J].Blood, 2002, 99 (10) :3838-3843.

[25] CORCIONE A, BENVENUTO F, FERRETTI E, et al. Human mesenchymal stem cells modulate B-cell functions[J].Blood, 2006, 107 (1) :367-372.

[26] SOTIROPOULOU PA, PEREZ SA, GRITZAPIS AD, et al. Interactions between human mesenchymal stem cells and natural killer cells[J]. Stem Cells, 2006, 24 (1) :74-85.

[27] MILOSAVLJEVIC N, GAZDIC M, SIMOVIC MARKOVIC B, et al. Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells[J]. Liver Transpl, 2017, 23 (8) :1040-1050.

[28] LEE KC, LIN HC, HUANG YH, et al. Allo-transplantation of mesenchymal stem cells attenuates hepatic injury through IL1Ra dependent macrophage switch in a mouse model of liver disease[J]. J Hepatol, 2015, 63 (6) :1405-1412.

[29] BEYTH S, BOROVSKY Z, MEVORACH D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness[J]. Blood, 2005, 105 (5) :2214-2219.

[30] EOM YW, SHIM KY, BAIK SK. Mesenchymal stem cell therapy for liver fibrosis[J]. Korean J Intern Med, 2015, 30 (5) :580-589.

[31] WANG J, BIAN C, LIAO L, et al. Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms[J]. Hepatol Res, 2009, 39 (12) :1219-1228.

[32] MEIER RP, MAHOU R, MOREL P, et al. Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice[J]. J Hepatol, 2015, 62 (3) :634-641.

[33] JIN HJ, KWON JH, KIM M, et al. Downregulation of melanoma cell adhesion molecule (MCAM/CD146) accelerates cellular senescence in human umbilical cord blood-derived mesenchymal stem cells[J]. Stem Cells Transl Med, 2016, 5 (4) :427-439.

[34] SUTO EG, MABUCHI Y, SUZUKI N, et al. Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73 (+) population and exhibit efficacy after transplantation[J].2017, 7 (1) :4838.

[35] de WITTE SFH, MERINO AM, FRANQUESA M, et al. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease[J]. Stem Cell Res Ther, 2017, 8 (1) :140.

[36] POURGHOLAMINEJAD A, AGHDAMI N, BAHARVAND H, et al. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells[J]. Cytokine, 2016, 85:51-60.

[37] REN G, ZHAO X, ZHANG L, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression[J]. J Immunol, 2010, 184 (5) :2321-2328.

[38] 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.

[39] 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.

[40] WANG K, LI Y, ZHU T, et al. Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure[J]. Stem Cell Res Ther, 2017, 8 (1) :162.

[41] MA HC, SHI XL, REN HZ, et al. Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration[J]. World J Gastroenterol, 2014, 20 (40) :14884-14894.

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