间充质干细胞治疗肝脏疾病的研究进展*

doi:10.3969/j.issn.1672-5069.2010.06.025

摘要/Abstract

摘要： 间充质干细胞（MSCs）可应用于治疗急性肝衰竭、终末期肝病和遗传代谢性肝病，旁分泌机制是其治疗肝病的重要机制。MSCs还可以通过调节免疫功能减轻炎症反应、抗肝细胞凋亡、抗肝纤维化、促进内源性肝干细胞分化和刺激内源性肝细胞增殖、促进血管增生等修复肝组织。进一步阐明MSCs的治疗机制，合理设计随机双盲对照临床试验，明确干细胞移植可能的副作用，是其广泛应用于临床的前提。

林沪,陈黎明,施明,王福生. 间充质干细胞治疗肝脏疾病的研究进展*[J]. 实用肝脏病杂志, 2010, 13(6): 460-463.

[1] PAREKKADAN B，VAN POLL D，SUGANUMA K，et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure[J]. PLoS ONE，2007，2（9）:e941.
[2] BANAS A，TERATANI T，YAMAMOTO Y，et al. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure[J]. J Gastroenterol Hepatol，2009，24（1）:70-77.
[3] ALISON MR，ISLAM S，LIM S. Stem cells in liver regeneration，fibrosis and cancer:the good，the bad and the ugly[J]. J Pathol，2009，217（2）:282-298.
[4] YAGI H，PAREKKADAN B，SUGANUMA K，et al. Long term superior performance of a stem cell/hepatocyte device for the treatment of acute liver failure[J]. Tissue Eng Part A，2009，15（11）:3377-3388.
[5] KUO TK，HUNG SP，CHUANG CH，et a1. Stem cell therapy for liver disease:parameters governing the success of using bone marrow mesenchymal stem cells[J]. Gastroenterology，2008，134（7）:2111-2121.
[6] BANAS A，TERATANI T，YAMAMOTO Y，et al. IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury[J]. Stem Cells，2008，26（10）:2705-2712.
[7] MOHAMADNEJAD M，ALIMOGHADDAM K， MOHYEDDIN-BONAB M，et al. Phase I trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated cirrhosis[J]. Arch Iran Med，2007，10（4）:459-466.
[8] KHARAZIHA P，HELLSTR e M 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.
[9] MIRANDA PS，BOSMA PJ. Towards liver-directed gene therapy for Crigler-Najjar syndrome[J]. Curr Gene Ther， 2009，9（2）:72-82.
[10] KHAN AA，PARVEEN N，MAHABOOB VS，et al. Treatment of Crigler-Najjar syndrome type 1 by hepatic progenitor cell transplantation:a simple procedure for management of hyperbilirubinemia[J]. Transplant Proc，2008，40（4）:1148-1150.
[11] FROSSARD V，KETTERER N，ROSSELET A，et al. Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis:a single-centre experience[J]. Ann Hematol，2009，88（7）:681-685.
[12] ZHOU P，HOHM S，OLUSANYA Y，et al. Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a novel model[J]. Hepatology，2009，49（6）:1992-2000.
[13] FERREIRA E，POTIER E，LOGEART-AVRAMOGLOU D，et al. Optimization of a gene electrotransfer method for mesenchymal stem cell transfection[J]. Gene Ther，2008，15（7）:537-544.
[14] ORTIZ LA，DUTREIL M，FATTMAN C，et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury[J]. Proc Natl Acad Sci USA，2007，104（26）:11002-11007.
[15] VAN POLL D，PAREKKADAN B，CHO CH，et al. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo[J]. Hepatology，2008，47（5）:1634-1643.
[16] TSAI PC，FU TW，CHEN YM，et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis[J]. Liver Transpl，2009，15（5）:484-495.
[17] PAREKKADAN B，VAN POLL D，MEGEED Z，et al. Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells[J]. Biochem. Biophys Res Commun，2007，363（2）:247-252.
[18] HIGASHIYAMA R，INAGAKI Y，HONG YY，et al. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice[J]. Hepatology，2007，45（1）:213-222.
[19] CARVALHO AB，QUINTANILHA LF，DIAS JV，et al. Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury[J]. Stem Cells，2008，26（5）:1307-1314.
[20] WANG Y，WEIL BR，HERRMANN JL，et al. MEK， p38 and PI-3K mediate cross talk between EGFR and TNFR in enhancing hepatocyte growth factor production from human mesenchymal stem cells[J]. Am J Physiol Cell Physiol，2009，297（5）:C1284-1293.
[21] WANG Y，WANG M，ABARBANELL AM，et al. MEK mediates the novel cross talk between TNFR2 and TGF-EGFR in enhancing vascular endothelial growth factor （VEGF）secretion from human mesenchymal stem cells[J]. Surgery，2009，146（2）:198-205.
[22] CRISOSTOMO PR，WANG Y，MARKEL TA，et al. Human mesenchymal stem cells stimulated by TNF-alpha， LPS，or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism[J]. Am J Physiol Cell Physiol，2008，294（3）:C675-682.
[23] AURICH H，SGODDA M，KALTWASSER P，et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo[J]. Gut，2009，58（4）:570-581.
[24] BONORA-CENTELLES A，JOVER R，MIRABET V，et al. Sequential hepatogenic trans-differentiation of adipose tissue-derived stem cells:relevance of different extracellular signaling molecules，transcription factors involved and expression of new key marker genes[J]. Cell Transplant， 2009，18（12）:1319-1340.
[25] BANAS A，TERATANI T，YAMAMOTO Y，et al. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure[J]. J Gastroenterol Hepatol，2009，24（1）:70-77.
[26] DENG X，CHEN YX，ZHANG X，et al. Hepatic stellate cells modulate the differentiation of bone marrow mesenchymal stem cells into hepatocyte-like cells[J]. J Cell Physiol，2008，217（1）:138-144.
[27] POTAPOVA，IA，GAUDETTE GR，BRINK PR，et al. Mesenchymal stem cells support migration，extracellular matrix invasion，proliferation and survival of endothelial cells in vitro[J]. Stem Cells，2007，25（7）:1761-1768.
[28] SADAT S，GEHMERT S，SONG YH，et al. The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF[J]. Biochem Biophys Res Commun，2007， 363（3）:674.
[29] SHAFRITZ DA，OERTEL M，MENTHENA A，et al. Liver stem cells and prospects for liver reconstitution by transplanted cells[J]. Hepatology，2006，43（2 Suppl 1）:S89-98.
[30] MATUSHANSKY I，HERNANDO E，SOCCI ND，et al. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway[J]. J Clin Invest，2007，117（11）:3248-3257.
[31] SUNDIN M，ORVELL C，RASMUSSON I，et al. Mesenchymal stem cells are susceptible to human herpes viruses，but viral DNA cannot be detected in the healthy seropositive individual[J]. Bone Marrow Transplant，2006，37（11）:1051-1059.
[32] BREITBACH M，BOSTANI T，ROELL W，et al. Potential risks of bone marrow cell transplantation into infarcted hearts[J]. Blood，2007，110（4）:1362-1369.

间充质干细胞治疗肝脏疾病的研究进展*

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	鲍应军, 任伟新. 门静脉血栓介入治疗研究进展[J]. 实用肝脏病杂志, 2019, 22(6): 768-769.
[2]	中国研究型医院学会肝病专业委员会, 中国医师协会脂肪性肝病专家委员会. 脂肪性肝病诊疗规范化的专家建议（2019年修订版）[J]. 实用肝脏病杂志, 2019, 22(6): 787-792.
[3]	. 肝纤维化诊断及治疗共识（2019年）[J]. 实用肝脏病杂志, 2019, 22(6): 793-803.
[4]	高磊, 曹蕾, 王瑞芳, 冯丹丹, 薛娟. 人脐带间充质干细胞移植对酒精性肝损伤大鼠的保护作用^*[J]. 实用肝脏病杂志, 2019, 22(6): 812-815.
[5]	石莹莹, 王元喜. 替比夫定联合阿德福韦酯治疗慢性乙型肝炎患者效果及其对肾功能的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 820-823.
[6]	邢欣, 魏重操, 周咪咪, 李小玲, 邓江, 鲁晓岚. 牛磺熊去氧胆酸与熊去氧胆酸治疗非酒精性脂肪性肝病患者疗效和安全性的Meta分析[J]. 实用肝脏病杂志, 2019, 22(6): 852-855.
[7]	段楚瑶, 陈庆山, 汪黎明, 贺晓琪. 熊去氧胆酸治疗妊娠期肝内胆汁淤积症患者疗效研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 864-867.
[8]	陈梅梅, 段晓燕, 曹海霞, 丁雯瑾. 复方鳖甲软肝片治疗原发性胆汁性肝硬化患者疗效分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 880-883.
[9]	马雅琼, 李芝兰, 夏冰. 早期肠内营养联合微生态制剂治疗肝性脑病患者肠道菌群的改变^*[J]. 实用肝脏病杂志, 2019, 22(6): 892-895.
[10]	冯文广, 姜伟, 宋国军. PPV指导术中液体治疗对行肝部分切除术治疗的肝内胆管结石患者术后并发症发生的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 912-915.
[11]	黎秋曦, 贾健锋, 黄锐. 区段肝蒂肝切除术与B超引导下肝切除术治疗肝胆管结石患者临床价值分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 916-919.
[12]	李传杰, 徐静, 王亮亮, 潘劲劲, 刘波. 恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究[J]. 实用肝脏病杂志, 2019, 22(6): 928-929.
[13]	张瑞, 王剑, 陈世耀. 肝硬化门脉高压症并发血栓形成机制和治疗研究进展^*[J]. 实用肝脏病杂志, 2019, 22(6): 930-933.
[14]	梁巨波, 苗琪, 马雄. 胆管细胞型胆汁淤积诊治进展[J]. 实用肝脏病杂志, 2019, 22(6): 941-943.
[15]	中华医学会肝病学分会, 中华医学会消化病学分会. 终末期肝病临床营养指南[J]. 实用肝脏病杂志, 2019, 22(5): 624-635.