干细胞诱导分化为肝细胞调控机制研究进展

doi:10.3969/j.issn.2095-378X.2017.03.013

摘要/Abstract

摘要： 干细胞(stem cell)是一类可自我复制的多潜能细胞。目前发现,通过体外诱导多种干细胞可分化为肝样细胞,并有肝细胞的表面标记及功能。肝移植为终末期肝病的最有效治疗方式,但面临供肝不足、费用大、长期免疫治疗等诸多限制。因此,干细胞在治疗终末期肝病方面显现出潜在的应用价值。文章重点综述干细胞分化为类肝细胞的调控机制进展。

关键词: 干细胞, 分化, 调节机制, 肝细胞

Abstract: Stem cells have the potential for self-renewal and multi-directional differentiation.Experiments have proven that stem cells can differentiate into hepatocyte-like cells under certain conditions,with hepatocyte markers and functions.Liver transplantation is the only effective and curative way for end-stage liver disease,but is limited by a shortage of donor organs,high costs of surgery,long-term immune therapy,and so on.In light of that,stem cells are of potential application value in the treatment of end-stage liver disease.This review focused on the regulatory mechanisms of stem cells differentiated into hepatocyte-like cells.

Key words: Stem cells, Differentiation, Regulatory mechanism, Hepatocyte-like cells

中图分类号:

R329.2⁺1

肖帅, 施宝民. 干细胞诱导分化为肝细胞调控机制研究进展[J]. 外科研究与新技术, 2017, 6(3): 189-192.

XIAO Shuai, SHI Baomin. Progress on regulatory mechanism of stem cells differentiated into hepatocyte-like cells[J]. Surgical Research and New Technique, 2017, 6(3): 189-192.

参考文献

[1] Duan BW,Lu SC,Wang ML,et al.Liver transplantation in acute-on-chronic liver failure patients with high model for end-stage liver disease (MELD) scores:a single center experience of 100 consecutive cases[J].J Surg Res,2013,183(2):936-943.
[2] 郭晓霞,贺福初.胚胎干细胞的研究与利用[J].科学通报,2000,45(5):467-474.
[3] 赵紫敬,程黎明.诱导性多功能干细胞在脊髓损伤干细胞治疗中的研究进展[J].外科研究与新技术,2013,2(1):52-58.
[4] Girlovanu M,Susman S,Soritau O,et al.Stem cells-biological update and cell therapy progress[J].Clin Med,2015,88(3):265-271.
[5] 张鹏,朱晓峰,焦兴元.卵圆细胞的生物学特性及其与原发性肝癌的关系[J].中国普外基础与临床杂志,2015,22(4):494-498.
[6] 杨志云,王宪波,殷飞,等.肝卵圆细胞——肝干细胞研究进展[J].中国肝脏病杂志(电子版),2010,2(1):52-55.
[7] Li Y,Zhao LJ,Xia FZ,et al.Transdifferentiation of hepatic oval cells into pancreatic islet beta-cells[J].Front Biosci (Landmark Ed),2012,17(1):2391-2395.
[8] Wang W,Du Z,Yan J,et al.Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts:involvement of C-Jun N-terminal kinase,cyclin D1,and NF-kappaB[J].PLoS One,2014,9(12):e112532.
[9] Ivey KN,Muth A,Arnold J,et al.MicroRNA regulation of cell lineages in mouse and human embryonic stem cells[J].Cell Stem Cell,2008,2(3):219-229.
[10] Cui L,Shi Y,Zhou X,et al.A set of microRNAs mediate direct conversion of human umbilical cord lining-derived mesenchymal stem cells into hepatocytes[J].Cell Death Dis,2013,4(11):e918.
[11] Cui L,Zhou X,Li J,et al.Dynamic microRNA profiles of hepatic differentiated human umbilical cord lining-derived mesenchymal stem cells[J].PLoS One.2012,7(9):e44737.
[12] Thakral S,Ghoshal K.miR-122 is a unique molecule with great potential in diagnosis,prognosis of liver disease,and therapy both as miRNA mimic and antimir[J].Curr Gene Ther,2015,15(2):142-150.
[13] Lagos-Quintana M,Rauhut R,Yalcin A,et al.Identification of tissue-specific microRNAs from mouse[J].Curr Biol,2002,12(9):735-739.
[14] Doddapaneni R,Chawla YK,Das A,et al.Overexpression of microRNA-122 enhances in vitro hepatic differentiation of fetal liver-derived stem/progenitor cells[J].J Cell Biochem,2013,114(7):1575-1583.
[15] Chien Y,Chang YL,Chien CS,et al.Synergistic effects of carboxymethyl-hexanoyl chitosan,cationic polyurethane-short branch PEI in miR122 gene delivery:accelerated differentiation of iPSCs into mature hepatocyte-like cells and improved stem cell therapy in a hepatic failure model[J].Acta Biomater,2015,13(2):228-244.
[16] Davoodian N,Lotfi AS,Soleimani M,et al.MicroRNA-122overexpression promotes hepatic differentiation of human adipose tissue-derived stem cells[J].J Cell Biochem.2014,115(9):1582-1593.
[17] Yahoo N,Pournasr B,Rostamzadeh J,et al.Forced expression of Hnf4a induces hepatic gene activation through directed differentiation[J].Biochem Biophys Res Commun,2016,476(4):313-318.
[18] Laudes M.Role of WNT signalling in the determination of human mesenchymal stem cells into preadipocytes[J].J Mol Endocrinol,2011,46(2):R65-72.
[19] Su N,Thiaville MM,Awad K,et al.Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor-4-independent pathway[J].Hepatology,2009,50(1):282-290.
[20] Liu T,Zhang S,Xiang D,et al.Induction of hepatocyte-like cells from mouse embryonic stem cells by lentivirus-mediated constitutive expression of Foxa2/Hnf4a[J].J Cell Biochem,2013,114(11):2531-2541.
[21] Chen KT,Pernelle K,Tsai YH,et al.,Liver X receptor alpha (LXRalpha/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4alpha[J].J Hepatol,2014,61(6):1276-1286.
[22] Hua M,Zhang W,Li W,et al.Molecular mechanisms regulating the establishment of hepatocyte polarity during human hepatic progenitor cell differentiation into a functional hepatocyte-like phenotype[J].J Cell Sci,2012,125(Pt 23):5800-5810.
[23] Kondo Y,Iwao T,Yoshihashi S,et al.Histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells[J].PLoS One,2014,9(8):e104010.
[24] Dong X,Pan R,Zhang H,et al.Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells[J].PLoS One,2013,8(5):e63405.
[25] Möbus S,Yang D,Yuan Q,et al.MicroRNA-199a-5p inhibition enhances the liver repopulation ability of human embryonic stem cell-derived hepatic cells[J].J Hepatol,2015,62(1):101-110.
[26] Yin L,Zhu Y,Yang J,et al.Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro[J].Mol Med Rep,2015,11(3):1722-1732.