title: Induced pluripotent stem cells as a source of hepatocytes.
abstract: During the past decade, a series of discoveries has established the potential of the so called terminally differentiated cells to transition to more primitive progenitor cells. The dramatic demonstration of the ability to reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) that can then give rise to cells of all three germ layers has opened the possibility of generating virtually any cell type in culture, from any given individual. Taking advantage of these concepts, researchers have generated iPSCs by reprogramming a wide variety of somatic cells. In addition to their practical implications, these studies have provided crucial insights into the mechanism of cell plasticity that underlies the transition from one cell type to another. Using concepts derived from research on embryological development, investigators have differentiated iPSCs to cells resembling hepatocytes in many ways. Such hepatocyte-like cells could be of enormous value in disease modeling, drug discovery and regenerative medicine. However, the currently available methods do not yield cells that fully reproduce the characteristics of adult primary hepatocytes. Thus generating hepatocytes from iPSCs is very much a work in progress. In addition to chronicling these exciting developments, this review will discuss the emergent new approaches to generating iPSCs, improving their differentiation to hepatocyte-like cells and maintaining the hepatocyte-like cells in culture for longer survival and better function.
authors: Department of Medicine (Division of Gastroenterology and Hepatology), Albert Einstein College of Medicine, New York ; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York.
authors: Vanessa
authors: V
authors: Sauer
authors: Department of Medicine (Division of Gastroenterology and Hepatology), Albert Einstein College of Medicine, New York ; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York ; Department of Genetics, Albert Einstein College of Medicine, New York.
authors: Namita
authors: N
authors: Roy-Chowdhury
authors: Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York ; Department of Radiation Oncology, Albert Einstein College of Medicine, New York.
authors: Chandan
authors: C
authors: Guha
authors: Department of Medicine (Division of Gastroenterology and Hepatology), Albert Einstein College of Medicine, New York ; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York ; Department of Genetics, Albert Einstein College of Medicine, New York.
authors: Jayanta
authors: J
authors: Roy-Chowdhury
keywords: directed differentiation; hepatocyte-like cells; iPS; reprogramming
references: Mech Dev. 2011 Sep-Dec;128(7-10):412-27
references: 21855631
references: Cell Stem Cell. 2011 Apr 8;8(4):376-88
references: 21474102
references: Adv Cancer Res. 2003;88:53-99
references: 12665053
references: Nat Biotechnol. 2009 May;27(5):459-61
references: 19363475
references: PLoS One. 2011;6(7):e21780
references: 21760905
references: PLoS One. 2010 Dec 30;5(12):e14397
references: 21209933
references: Methods. 2013 Jan;59(1):59-70
references: 22503774
references: BMC Dev Biol. 2010 Aug 03;10:81
references: 20682060
references: Hepatology. 2010 May;51(5):1810-9
references: 20432258
references: Biol Cell. 2008 Jul;100(7):387-98
references: 18549352
references: EMBO J. 1999 Apr 15;18(8):2127-36
references: 10205167
references: Nature. 2009 Apr 9;458(7239):766-70
references: 19252478
references: Biotechnology. 1992;20:363-90
references: 1318139
references: Nature. 1995 Feb 23;373(6516):699-702
references: 7854452
references: Science. 2008 Nov 7;322(5903):949-53
references: 18845712
references: Mol Ther. 2012 Jan;20(1):127-37
references: 22068426
references: Cell Stem Cell. 2010 Jul 2;7(1):15-9
references: 20621044
references: Mol Ther. 2011 Feb;19(2):400-7
references: 21102561
references: Stem Cells. 2012 Apr;30(4):631-42
references: 22893457
references: PLoS One. 2009 Jun 30;4(6):e6082
references: 19564924
references: Cell Stem Cell. 2010 Nov 5;7(5):618-30
references: 20888316
references: Cell. 2006 Aug 25;126(4):663-76
references: 16904174
references: PLoS One. 2010 Nov 12;5(11):e15456
references: 21103392
references: Nat Methods. 2010 Mar;7(3):197-9
references: 20139967
references: Nat Genet. 2008 Dec;40(12):1478-83
references: 18978791
references: Cell. 2009 Mar 6;136(5):964-77
references: 19269371
references: Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(8):348-62
references: 19838014
references: Dev Biol. 2009 Jun 15;330(2):286-304
references: 19358838
references: J Biol Chem. 2011 Feb 11;286(6):4760-71
references: 21138846
references: Stem Cells Int. 2012;2012:564612
references: 22550511
references: Exp Hematol. 2003 Nov;31(11):1007-14
references: 14585362
references: J Am Soc Nephrol. 2011 Jul;22(7):1221-8
references: 21636641
references: Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):61-74
references: 16922653
references: Cell. 2008 Feb 22;132(4):661-80
references: 18295582
references: Cell Stem Cell. 2011 Jul 8;9(1):17-23
references: 21726830
references: EMBO J. 2001 Apr 17;20(8):1974-83
references: 11296230
references: FEBS Lett. 2001 Mar 9;492(1-2):90-4
references: 11248243
references: Mol Cell Biol. 1995 Jan;15(1):141-51
references: 7799920
references: Nature. 2009 Aug 27;460(7259):1136-9
references: 19668188
references: Hepatology. 2011 Feb;53(2):604-17
references: 21274881
references: J Virol. 2000 Jul;74(14):6564-9
references: 10864670
references: Virus Res. 2002 Jun;86(1-2):33-8
references: 12076827
references: Exp Cell Res. 2013 Oct 15;319(17):2535-44
references: 23954819
references: Nat Commun. 2013;4:1847
references: 23673632
references: J Stem Cell Res Ther. 2012 Aug 15;Suppl 10(8):1-7
references: 25364624
references: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15720-5
references: 19805220
references: Adv Exp Med Biol. 2010;695:1-13
references: 21222195
references: Nature. 2009 Oct 1;461(7264):649-3
references: 19718018
references: Science. 2009 May 8;324(5928):797-801
references: 19325077
references: Nat Biotechnol. 2008 Nov;26(11):1276-84
references: 18931654
references: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8918-22
references: 19458047
references: Stem Cells. 2009 Nov;27(11):2667-74
references: 19697349
references: Mol Ther. 2002 Apr;5(4):340-4
references: 11945059
references: Nat Med. 2010 Jul;16(7):814-20
references: 20543851
references: Cell Stem Cell. 2010 Jul 2;7(1):20-4
references: 20621045
references: Cell. 2007 Nov 30;131(5):861-72
references: 18035408
references: Hepatology. 2010 May;51(5):1754-65
references: 20301097
references: Recent Pat DNA Gene Seq. 2012 Aug;6(2):82-90
references: 22670608
references: Stem Cell Rev. 2011 Sep;7(3):518-31
references: 21210253
references: Genes Dev. 1996 Jul 1;10(13):1670-82
references: 8682297
references: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7598-602
references: 8052626
references: Biochemistry. 2005 Jan 11;44(1):138-48
references: 15628854
references: Mol Cell Biol. 2008 Oct;28(20):6426-38
references: 18710938
references: Cold Spring Harb Symp Quant Biol. 2008;73:101-10
references: 19329573
references: J Gene Med. 2008 Nov;10(11):1176-89
references: 18773501
references: Cell Stem Cell. 2009 Oct 2;5(4):434-41
references: 19796623
references: Cell. 1988 Dec 23;55(6):1189-93
references: 2849510
references: Cancer Res. 2009 May 15;69(10):4093-6
references: 19435891
references: Cell. 2008 Sep 5;134(5):877-86
references: 18691744
references: J Biol Chem. 2011 May 13;286(19):17359-64
references: 21454525