title: Signalling pathways involved in the process of mesenchymal stem cells differentiating into hepatocytes.
abstract: End-stage liver disease can be the termination of acute or chronic liver diseases, with manifestations of liver failure; transplantation is currently an effective treatment for these. However, transplantation is severely limited due to the serious lack of donors, expense, graft rejection and requirement of long-term immunosuppression. Mesenchymal stem cells (MSCs) have attracted considerable attention as therapeutic tools as they can be obtained with relative ease and expanded in culture, along with features of self-renewal and multidirectional differentiation. Many scientific groups have sought to use MSCs differentiating into functional hepatocytes to be used in cell transplantation with liver tissue engineering to repair diseased organs. In most of the literature, hepatocyte differentiation refers to use of various additional growth factors and cytokines, such as hepatocyte growth factor (HGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), oncostatin M (OSM) and more, and most are involved in signalling pathway regulation and cell-cell/cell-matrix interactions. Signalling pathways have been shown to play critical roles in embryonic development, tumourigenesis, tumour progression, apoptosis and cell-fate determination. However, mechanisms of MSCs differentiating into hepatocytes, particularly signalling pathways involved, have not as yet been completely illustrated. In this review, we have focused on progress of signalling pathways associated with mesenchymal stem cells differentiating into hepatocytes along with the stepwise differentiation procedure.
authors: BRC, First Hospital of Kun Ming, Kun Ming, 650011, China; Lorraine University and CNRS UMR 7365, Medical College, Vandoeuvre-lès-Nancy, 54500, France.
authors: Jun-Song
authors: JS
authors: Ye
authors: Xiao-San
authors: XS
authors: Su
authors: J-F
authors: JF
authors: Stoltz
authors: N
authors: N
authors: de Isla
authors: Lei
authors: L
authors: Zhang
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D058625:End Stage Liver Disease / Q000628:therapy; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D015398:Signal Transduction; D023822:Tissue Engineering
references: Biochem Biophys Res Commun. 2011 Apr 8;407(2):295-300
references: 21382341
references: Exp Cell Res. 2013 Oct 15;319(17):2535-44
references: 23954819
references: Zygote. 2014 Aug;22(3):411-8
references: 23506698
references: J Hepatol. 2013 Jan;58(1):65-72
references: 22960426
references: Int Rev Cytol. 2007;259:49-111
references: 17425939
references: N Engl J Med. 1998 Jun 11;338(24):1741-51
references: 9624195
references: Curr Opin Mol Ther. 2009 Aug;11(4):364-74
references: 19649981
references: Dev Biol. 2004 Aug 15;272(2):432-47
references: 15282159
references: Arch Iran Med. 2011 Jul;14(4):244-9
references: 21726099
references: Stem Cells. 2004;22(3):405-14
references: 15153617
references: J Clin Periodontol. 2012 Dec;39(12):1174-82
references: 23005571
references: Theriogenology. 2010 Nov;74(8):1341-8
references: 20688373
references: Biol Open. 2013 Jan 15;2(1):30-6
references: 23336074
references: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009 Jun;31(3):330-4
references: 19621519
references: N Engl J Med. 2008 Mar 20;358(12):1302
references: 18354113
references: J Hepatol. 2013 Jan;58(1):181-3
references: 22902547
references: Dev Biol. 2008 Jul 15;319(2):234-47
references: 18513713
references: PLoS One. 2010 Oct 27;5(10):e13650
references: 21048969
references: J Recept Signal Transduct Res. 2013;33(1):28-36
references: 23327602
references: Res Vet Sci. 2014 Feb;96(1):95-101
references: 24377415
references: Arch Plast Surg. 2012 Nov;39(6):593-9
references: 23233883
references: J Cell Biochem. 2007 Jan 1;100(1):29-42
references: 16888815
references: J Zhejiang Univ Sci B. 2013 Nov;14(11):961-72
references: 24190442
references: Nat Protoc. 2010 Jul;5(7):1324-36
references: 20595960
references: Hepatology. 2005 May;41(5):956-67
references: 15841465
references: Stem Cells. 2006 Jan;24(1):23-33
references: 16100005
references: Hepatology. 2008 Jan;47(1):247-58
references: 18038450
references: Exp Cell Res. 2004 Jan 15;292(2):252-64
references: 14697333
references: Stem Cell Res. 2013 Jul;11(1):563-73
references: 23644508
references: Eur Cytokine Netw. 2000 Sep;11(3):443-51
references: 11022130
references: Zygote. 2011 Aug;19(3):191-7
references: 21303586
references: Hepatology. 2010 May;51(5):1754-65
references: 20301097
references: Development. 2007 Mar;134(6):1023-34
references: 17287255
references: Cell Transplant. 2002;11(5):435-41
references: 12382670
references: Exp Cell Res. 2009 Dec 10;315(20):3486-99
references: 19799897
references: J Biol Chem. 2012 Jun 29;287(27):22789-98
references: 22613727
references: Exp Cell Res. 2014 Feb 1;321(1):11-6
references: 23939346
references: Mucosal Immunol. 2014 May;7(3):656-69
references: 24172849
references: J Int Med Res. 2008 Jul-Aug;36(4):721-7
references: 18652768
references: Stem Cells Int. 2013;2013:762196
references: 23818908
references: FEBS Lett. 2001 Mar 9;492(1-2):90-4
references: 11248243
references: Cell Prolif. 2010 Oct;43(5):427-34
references: 20887549
references: Antioxid Redox Signal. 2013 Jan 20;18(3):239-49
references: 22657837
references: Clin Res Hepatol Gastroenterol. 2013 Dec;37(6):602-7
references: 24012221
references: Biol Pharm Bull. 2009 Feb;32(2):209-12
references: 19182377
references: Liver. 1999 Dec;19(6):481-8
references: 10661681
references: Hepatogastroenterology. 2012 Sep;59(118):1921-7
references: 22819913
references: J Cell Biol. 2000 Feb 7;148(3):567-78
references: 10662781
references: Br Med Bull. 2013;105:43-68
references: 23184854
references: Dev Biol. 2005 Apr 1;280(1):87-99
references: 15766750
references: J Exp Med. 2007 Aug 6;204(8):1973-87
references: 17664288
references: Am J Pathol. 2004 Jun;164(6):2229-40
references: 15161655
references: Breast Cancer Res Treat. 2012 Feb;132(1):153-64
references: 21584665
references: Stem Cells. 2007 Jan;25(1):29-38
references: 17204604
references: Cancer Biomark. 2012;11(4):161-71
references: 23144154
references: Cytotherapy. 2009;11(4):377-91
references: 19568970
references: Stem Cell Res Ther. 2011 Apr 04;2(2):16
references: 21463501
references: Development. 1998 Mar;125(6):1005-15
references: 9463347
references: In Vitro Cell Dev Biol Anim. 2006 Mar-Apr;42(3-4):83-8
references: 16759153
references: Biochem Biophys Res Commun. 2004 Jul 30;320(3):712-6
references: 15240106
references: Acta Obstet Gynecol Scand. 2008;87(12):1322-8
references: 18972232
references: Neuroscience. 2013 May 15;238:305-18
references: 23454369
references: Hepatology. 1995 Dec;22(6):1769-75
references: 7489987
references: Inflammation. 2012 Feb;35(1):138-42
references: 21274741
references: Biochem Biophys Res Commun. 2005 May 20;330(4):1153-61
references: 15823564
references: Xenotransplantation. 2010 May-Jun;17(3):181-7
references: 20636538
references: Clin Liver Dis. 2006 Feb;10(1):1-25, v
references: 16376792
references: Tissue Eng Part A. 2013 Feb;19(3-4):360-7
references: 23003670
references: Tissue Eng Part C Methods. 2010 Dec;16(6):1543-51
references: 20504066
references: In Vitro Cell Dev Biol Anim. 2013 Aug;49(7):515-23
references: 23708920
references: Hepatology. 2009 Jul;50(1):253-60
references: 19441100
references: Hepatology. 2005 Jun;41(6):1407-32
references: 15880505