自体骨髓干细胞治疗肝硬化的应用及管理

王邓; 孙航; 吴传新

doi:10.3969/j.issn.1001-5256.2019.04.042

自体骨髓干细胞治疗肝硬化的应用及管理

DOI: 10.3969/j.issn.1001-5256.2019.04.042

1. 重庆医科大学附属第二医院肝胆外科
2. 重庆医科大学附属第二医院病毒性肝炎研究所

基金项目:

国家自然科学基金面上项目(81871608)；

详细信息

中图分类号: R575.2
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出版历程
- 出版日期: 2019-04-20

Application and management of autologous bone marrow stem cells in treatment of liver cirrhosis

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University

Research funding:

摘要

摘要: 肝移植被认为是治疗肝硬化的最佳方式,但因供体不足、费用较高、免疫排斥等原因而受到限制。近年来骨髓干细胞在治疗肝硬化上展示出了广阔前景。目前已有大量临床试验表明自体骨髓干细胞治疗肝硬化是一种安全、有效的治疗方式,但其机制并不清楚,且治疗方案有多种选择。就骨髓干细胞治疗肝硬化的机制、骨髓干细胞输入通路、疗效评估指标、细胞输入剂量等进行综述。
- 肝硬化 /
- 骨髓移植 /
- 治疗学 /
- 综述
Abstract: Liver transplantation is considered the best method for the treatment of liver cirrhosis, but its clinical application is limited by the shortage of liver donors, high costs, and immunological rejection. In recent years, bone marrow stem cells ( BMSCs) has shown great prospects in the treatment of liver cirrhosis. Recent clinical studies have shown that BMSC therapy is a safe and effective treatment method for liver cirrhosis, but its mechanism remains unclear, and there are various treatment regimens. This article reviews the mechanism of BMSCs in the treatment of liver cirrhosis, route of BMSC delivery, indices for therapeutic effect evaluation, and dose of BMSCs.
- liver cirrhosis /
- bone marrow transplantation /
- therapeutics /
- review

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参考文献(43)

[1]LOZANO R, NAGHAVI M, FOREMAN K, et al. Global and regional mortality from 235 causes of death for 20 age groups in1990 and 2010:A systematic analysis for the Global Burden of Disease Study 2010[J]. Lancet, 2012, 380 (9895) :2095-2128.

[2]GUO Y, CHEN B, CHEN LJ, et al. Current status and future prospects of mesenchymal stem cell therapy for liver fibrosis[J]. J Zhejiang Univ Sci B, 2016, 17 (11) :831-841.

[3]DAI LJ, LI HY, GUAN LX, et al. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis[J]. Stem Cell Res, 2009, 2 (1) :16-25.

[4]GOLDBERG D, FRENCH B, TROTTER J, et al. Underreporting of liver transplant waitlist removals due to death or clinical deterioration:Results at four major centers[J]. Transplantation, 2013, 96 (2) :211-216.

[5]TERAI S, TAKAMI T, YAMAOTO N, et al. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells[J]. Tissue Eng Part B Rev, 2014, 20 (3) :206-210.

[6]LEVICAR N, PAI M, HABIB NA, et al. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+cells in patients with chronic liver disease[J].Cell Prolif, 2008, 41 (Suppl 1) :115-125.

[7]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.

[8]ZHAO DC, LEI JX, CHEN R, et al. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats[J]. World J Gastroenterol, 2005, 11 (22) :3431-3440.

[9]AQUINO JB, BOLONTRADE MF, GARCIA MG, et al. Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma[J]. Gene Ther, 2010, 17 (6) :692-708.

[10]LIU W, YU SY, YAN HZ, et al. Therapeutic effect of MSCs transplantation on rats with hepatic fibrosis[J]. Chin J Med Offic, 2017, 45 (9) :903-909. (in Chinese) 刘卫, 余森源, 严和中, 等.骨髓间质干细胞移植对肝纤维化模型大鼠治疗效果[J].临床军医杂志, 2017, 45 (9) :903-909.

[11]LYU SL, MA Y, DING TL. Bone marrow mesenchymal stem cells as therapy for hepatic fibrosis[J]. J Clin Hepatol, 2012, 28 (11) :819-823. (in Chinese) 吕素莉, 马勇, 丁体龙.骨髓间充质干细胞移植在肝纤维化治疗中的应用[J].临床肝胆病杂志, 2012, 28 (11) :819-823.

[12]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.

[13]LYRA AC, SOARES MB, DA SL, et al. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease[J]. World J Gastroenterol, 2007, 13 (7) :1067-1073.

[14]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.

[15]ZHANG Z, WANG FS. Stem cell therapies for liver failure and cirrhosis[J]. J Hepatol, 2013, 59 (1) :183-185.

[16]FARBER E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylaminofluorene, and 3'-methyl-4-dimethylaminoazobenzene[J]. Cancer Res, 1956, 16 (2) :142-148.

[17]GOFF JP, SHIELDS DS, PETERSEN BE, et al. Synergistic effects of hepatocyte growth factor on human cord blood CD34+progenitor cells are the result of c-met receptor expression[J]. Stem Cells, 1996, 14 (5) :592-602.

[18]OH SH, MIYAZAKI M, KOUCHI H, et al. Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro[J]. Biochem Biophys Res Commun, 2000, 279 (2) :500-504.

[19]LANGE C, BASSLER P, LIOZNOV MV, et al. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells[J]. World J Gastroenterol, 2005, 11 (29) :4497-4504.

[20]AZIZ MTA, ATTA HM, MAHFOUZ S, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis[J]. Clin Biochem, 2007, 40 (12) :893-899.

[21]ZHAO JW. Research progresses in treatment of liver fibrosis and cirrhosis using bone marrow stem cells[J]. Progr Physiolog Sci, 2017, 48 (2) :88-93. (in Chinese) 赵经文.应用骨髓干细胞治疗肝硬化研究进展[J].生理科学进展, 2017, 48 (2) :88-93.

[22]SUN YG, KIM JK, BYUN JS, et al. CD11b+Gr1+bone marrow cells ameliorate liver fibrosis by producing interleukin-10in mice[J]. Hepatology, 2012, 56 (5) :1902-1912.

[23]WALCZAK P, ZHANG J, GILAD AA, et al. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia[J]. Stroke, 2008, 39 (5) :1569-1574.

[24]KIDD S, SPAETH E, DEMBINSKI JL, et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging[J]. Stem Cells, 2009, 27 (10) :2614-2623.

[25]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.

[26]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.

[27]LAIO X, ANCHENG JY, ZHOU QJ, et al. Therapeutic effect of autologous bone marrow-derived liver stem cells transplantation in hepatitis B virus-induced liver cirrhosis[J]. Hepatogastroenterology, 2013, 60 (123) :406-409.

[28]SALAMA H, ZEKRI AR, BAHNASSY AA, et al. Autologous CD34+and CD133+stem cells transplantation in patients with end stage liver disease[J]. World J Gastroenterol, 2010, 16 (42) :5297-5305.

[29]HUANG ZH, ZENG S, OUYANG M, et al. Treatment of acute liver injury by intrasplenic transplantation of hepatic stem cells combined with heparin in rats[J]. J Cent South Univ:Med Sci, 2011, 36 (5) :411-416. (in Chinese) 黄增辉, 曾珊, 欧阳淼, 等.肝素联合肝干细胞经脾移植治疗SD大鼠急性肝损伤[J].中南大学学报:医学版, 2011, 36 (5) :411-416.

[30]ZHANG LX, LI Y, WANG LM. Bone marrow mesenchymal stem cell transplantation via different approaches in treatment of liver cirrhosis in mice[J]. J Clin Hepatol, 2016, 32 (10) :1906-1910. (in Chinese) 张丽霞, 李莹, 王黎明, 等.不同途径移植骨髓间充质干细胞治疗肝硬化小鼠的效果比较[J].临床肝胆病杂志, 2016, 32 (10) :1906-1910.

[31]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.

[32]SALAMA H, ZEKRI AR, MEDHAT E, et al. Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease[J]. Stem Cell Res Ther, 2014, 5 (3) :70.

[33]WU YZ, YANG L, ZHAI YF, et al. Therapeutic effect of autologous bone marrow mesenchymal stem cells on hepatic fibrosis, liver function, MELD score and 1-year survival rate in patients with decompensated hepatitis B[J]. Chin J Tissue Engineer Res, 2017, 21 (13) :2049-2055. (in Chinese) 吴玉卓, 杨乐, 翟玉峰, 等.自体骨髓间充质干细胞治疗乙型肝炎失代偿期患者:肝纤维化、肝功能、MELD评分及1年生存率分析[J].中国组织工程研究, 2017, 21 (13) :2049-2055.

[34]BAI YQ, YANG YX, YANG YG, et al. Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis[J]. World J Gastroenterol, 2014, 20 (26) :8660-8666.

[35]HUANG LW, LIU L, ZHOU J. The application value of indocyanine green clearance test in assessment of liver reserve function for patients with stem cell transplantation[J]. Chin J Gastroenterol Hepatol, 2012, 21 (11) :1047-1050. (in Chinese) 黄丽雯, 刘黎, 周健.吲哚菁绿清除试验在干细胞移植患者肝脏储备功能评估中的应用价值[J].胃肠病学和肝病学杂志, 2012, 21 (11) :1047-1050.

[36]XU L, GONG Y, WANG B, et al. Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis:Regulation of Treg/Th17 cells[J]. J Gastroenterol Hepatol, 2014, 29 (8) :1620-1628.

[37]LUK JM, WANG PP, LEE CK, et al. Hepatic potential of bone marrow stromal cells:Development of in vitro co-culture and intraportal transplantation models[J]. J Immunol Methods, 2005, 305 (1) :39-47.

[38]SHACKEL N, ROCKEY D. In pursuit of the“Holy Grail”stem cells, hepatic injury, fibrogenesis and repair[J]. Hepatology, 2005, 41 (1) :16-18.

[39]SAKAIDA I, TERAI S, YAMAMOTO N, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice[J]. Hepatology, 2004, 40 (6) :1304-1311.

[40]ONG SY, DAI H, LEONG KW. Inducing hepatic differentiation of human mesenchymal stem cells in peller culture[J]. Biomaterials, 2006, 27 (22) :4987-4097.

[41]LIU L, YAN Y, JIAN Z, et al. Curative effect of combined lamivudine, adefovir dipivoxil, and stem cell transplantation on decompensated hepatitis B cirrhosis[J]. Genet Mol Res, 2014, 13 (4) :9336-9342.

[42]WANG D, GUO XZ, LI HY, et al. Safety and efficacy of intravenous injection of granulocyte colony stimulating factor for mobilization of autologous bone marrow stem cells in patients with decompensated cirrhosis[J]. Chin J Cell Stem Cell, 2014, 4 (4) :232-235. (in Chinese) 王迪, 郭晓钟, 李宏宇, 等.粒细胞集落刺激因子对失代偿期肝硬化患者骨髓干细胞的动员效果及安全性观察[J].中华细胞与干细胞杂志, 2014, 4 (4) :232-235.

[43]TAYEB AH, DORRY EA, AMER N, et al. Autologous stem cells transplantation in egyptian patients with liver cirrhosis on top of hepatitis C virus[J]. Int J Stem Cells, 2015, 8 (2) :209-218.

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