title: Induced pluripotent stem cells--opportunities for disease modelling and drug discovery.
abstract: The ability to generate induced pluripotent stem cells (iPSCs) from patients, and an increasingly refined capacity to differentiate these iPSCs into disease-relevant cell types, promises a new paradigm in drug development - one that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSCs that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSCs can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling a 'disease in a dish' and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets and enhance the probability of clinical success of new drugs.
authors.affiliation: iPierian, 951 Gateway Blvd, South San Francisco, California 94080, USA.
authors.forename: Marica
authors.initials: M
authors.lastname: Grskovic
authors.forename: Ashkan
authors.initials: A
authors.lastname: Javaherian
authors.forename: Berta
authors.initials: B
authors.lastname: Strulovici
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000473:pathology
references.citation: Nat Biotechnol. 2009 Mar;27(3):275-80
references.pmid: 19252484
references.citation: Nature. 2009 Apr 9;458(7239):766-70
references.pmid: 19252478
references.citation: Hepatology. 2010 May;51(5):1810-9
references.pmid: 20432258
references.citation: Nature. 2007 Jul 19;448(7151):313-7
references.pmid: 17554338
references.citation: Trends Pharmacol Sci. 2010 Jan;31(1):36-45
references.pmid: 19896224
references.citation: Nat Rev Drug Discov. 2006 Oct;5(10):835-44
references.pmid: 17016424
references.citation: Blood. 2011 Jan 20;117(3):839-47
references.pmid: 21037085
references.citation: Cell Stem Cell. 2008 Jan 10;2(1):10-2
references.pmid: 18371415
references.citation: Nat Chem Biol. 2006 Aug;2(8):415-6
references.pmid: 16816845
references.citation: Nature. 2009 Jan 15;457(7227):277-80
references.pmid: 19098894
references.citation: Science. 2008 May 30;320(5880):1224-9
references.pmid: 18511691
references.citation: Nat Cell Biol. 2011 May;13(5):541-9
references.pmid: 21499256
references.citation: Nature. 2011 May 22;474(7351):399-402
references.pmid: 21602826
references.citation: Nature. 2010 Mar 11;464(7286):292-6
references.pmid: 20164838
references.citation: Nature. 2009 Oct 1;461(7264):649-3
references.pmid: 19718018
references.citation: Nature. 2010 Nov 18;468(7322):443-6
references.pmid: 21085180
references.citation: J Neurosci Methods. 1998 Dec 1;85(2):141-52
references.pmid: 9874150
references.citation: Pharmacol Rev. 2010 Dec;62(4):760-81
references.pmid: 21079043
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):157-62
references.pmid: 19109433
references.citation: Cell Res. 2011 Mar;21(3):518-29
references.pmid: 21243013
references.citation: Cell Stem Cell. 2010 May 7;6(5):407-11
references.pmid: 20452313
references.citation: Mol Ther. 2010 Jun;18(6):1192-9
references.pmid: 20407427
references.citation: Cell Res. 2011 Jan;21(1):205-12
references.pmid: 21135873
references.citation: J Biol Chem. 2010 Jun 18;285(25):19483-90
references.pmid: 20382743
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7613-8
references.pmid: 19383789
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15921-6
references.pmid: 20798034
references.citation: Nature. 2009 Jul 2;460(7251):53-9
references.pmid: 19483674
references.citation: BMC Dev Biol. 2010 Aug 03;10:81
references.pmid: 20682060
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Nature. 2010 Jun 10;465(7299):808-12
references.pmid: 20535210
references.citation: Science. 1998 Nov 6;282(5391):1145-7
references.pmid: 9804556
references.citation: Hum Mol Genet. 2009 Nov 15;18(22):4340-9
references.pmid: 19679563
references.citation: Science. 2009 May 8;324(5928):797-801
references.pmid: 19325077
references.citation: Nat Genet. 2009 Sep;41(9):968-76
references.pmid: 19668214
references.citation: Am J Med Genet A. 2006 Dec 1;140(23):2603-24
references.pmid: 16838330
references.citation: Cell Stem Cell. 2010 Jan 8;6(1):71-9
references.pmid: 20036631
references.citation: Nature. 2010 May 13;465(7295):175-81
references.pmid: 20418860
references.citation: N Engl J Med. 2007 Nov 22;357(21):2109-22
references.pmid: 17984165
references.citation: Science. 2000 Jan 28;287(5453):646-50
references.pmid: 10649997
references.citation: Nat Biotechnol. 2007 Oct;25(10):1177-81
references.pmid: 17724450
references.citation: Hum Mol Genet. 2005 Nov 1;14(21):3129-40
references.pmid: 16159889
references.citation: Cell Stem Cell. 2010 Oct 8;7(4):521-31
references.pmid: 20887957
references.citation: Cell Stem Cell. 2011 Feb 4;8(2):228-40
references.pmid: 21295278
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):267-80
references.pmid: 21362567
references.citation: N Engl J Med. 2010 Oct 7;363(15):1397-409
references.pmid: 20660394
references.citation: Science. 2008 Aug 29;321(5893):1218-21
references.pmid: 18669821
references.citation: Cell Stem Cell. 2007 Jun 7;1(1):55-70
references.pmid: 18371336
references.citation: Nat Biotechnol. 2008 Jan;26(1):101-6
references.pmid: 18059259
references.citation: Nat Rev Drug Discov. 2004 Aug;3(8):711-5
references.pmid: 15286737
references.citation: Cell Cycle. 2009 Dec;8(23):3822-30
references.pmid: 19887907
references.citation: Cell Stem Cell. 2011 Apr 8;8(4):434-44
references.pmid: 21458401
references.citation: Cell Host Microbe. 2008 Nov 13;4(5):495-504
references.pmid: 18976975
references.citation: Nat Rev Neurosci. 2009 Aug;10(8):597-609
references.pmid: 19584893
references.citation: Cell Stem Cell. 2011 Jan 7;8(1):31-45
references.pmid: 21185252
references.citation: Stem Cell Rev Rep. 2010 Dec;6(4):622-32
references.pmid: 20821352
references.citation: Blood. 2011 Aug 18;118(7):1801-5
references.pmid: 21628406
references.citation: Ann Neurol. 2011 Sep;70(3):402-9
references.pmid: 21721033
references.citation: Reprod Biomed Online. 2009 May;18(5):704-16
references.pmid: 19549452
references.citation: Cell Stem Cell. 2009 Oct 2;5(4):353-7
references.pmid: 19796614
references.citation: Stem Cells. 2009 Nov;27(11):2667-74
references.pmid: 19697349
references.citation: Biochem Biophys Res Commun. 2010 Mar 26;394(1):189-93
references.pmid: 20188704
references.citation: J Invest Dermatol. 2011 Apr;131(4):848-56
references.pmid: 21124339
references.citation: J Biol Chem. 2011 Feb 11;286(6):4760-71
references.pmid: 21138846
references.citation: Nat Biotechnol. 2010 Apr;28(4):371-7
references.pmid: 20351689
references.citation: In Vitro Cell Dev Biol Anim. 2010 Apr;46(3-4):376-85
references.pmid: 20217271
references.citation: J Neurosci. 2011 Apr 20;31(16):5970-6
references.pmid: 21508222
references.citation: Cell Stem Cell. 2011 Jun 3;8(6):663-75
references.pmid: 21624811
references.citation: Nat Biotechnol. 2008 Nov;26(11):1276-84
references.pmid: 18931654
references.citation: Blood. 2009 May 28;113(22):5476-9
references.pmid: 19299331
references.citation: Nat Genet. 2005 Oct;37(10):1099-103
references.pmid: 16142235
references.citation: Methods Mol Biol. 2010;636:207-18
references.pmid: 20336525
references.citation: Cell Stem Cell. 2011 Jun 3;8(6):633-8
references.pmid: 21620789
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2883-8
references.pmid: 18287077
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15720-5
references.pmid: 19805220
references.citation: N Engl J Med. 2004 Mar 4;350(10):1013-22
references.pmid: 14999113
references.citation: Nature. 2011 Mar 10;471(7337):225-9
references.pmid: 21240260
references.citation: Nature. 2009 Sep 3;461(7260):91-4
references.pmid: 19672243
references.citation: Cell. 2009 Mar 6;136(5):964-77
references.pmid: 19269371
references.citation: PLoS Biol. 2009 Feb 24;7(2):e42
references.pmid: 19243222
references.citation: Nature. 2009 Sep 17;461(7262):402-6
references.pmid: 19693009
references.citation: Nat Biotechnol. 2011 Mar;29(3):279-86
references.pmid: 21293464
references.citation: Reprod Biomed Online. 2009 Jul;19(1):106-13
references.pmid: 19573298
references.citation: Proc Natl Acad Sci U S A. 2011 May 24;108(21):8797-802
references.pmid: 21555586
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):472-6
references.pmid: 19481515
references.citation: PLoS One. 2010 Feb 01;5(2):e8975
references.pmid: 20126639
references.citation: Stem Cells. 2010 Apr;28(4):713-20
references.pmid: 20201064
references.citation: J Biol Chem. 2010 May 28;285(22):17209-17
references.pmid: 20212047
references.citation: J Cell Sci. 2009 Sep 1;122(Pt 17):3169-79
references.pmid: 19671662
references.citation: Hum Mol Genet. 2011 Sep 15;20(18):3653-66
references.pmid: 21685203
references.citation: Differentiation. 2010 Sep-Oct;80(2-3):123-9
references.pmid: 20510497
references.citation: Cell Stem Cell. 2010 Dec 3;7(6):651-5
references.pmid: 21112560
references.citation: Cell Stem Cell. 2009 Sep 4;5(3):332-42
references.pmid: 19733544
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4335-40
references.pmid: 20160098
references.citation: Stem Cells. 2010 Oct;28(10):1728-40
references.pmid: 20715179
references.citation: Cell Cycle. 2010 Mar 1;9(5):937-46
references.pmid: 20160486
references.citation: Stem Cells. 2009 Dec;27(12):2992-3000
references.pmid: 19839055
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15768-73
references.pmid: 19720998
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):135-8
references.pmid: 19631602
references.citation: Blood. 2009 Dec 24;114(27):5473-80
references.pmid: 19797525
references.citation: Blood. 2011 Aug 18;118(7):1797-800
references.pmid: 21708888
references.citation: ChemMedChem. 2006 Aug;1(8):761-82
references.pmid: 16902930
references.citation: PLoS Curr. 2010 Oct 28;2:RRN1193
references.pmid: 21037797
references.citation: Blood. 2011 Apr 7;117(14):e109-19
references.pmid: 21296996
references.citation: Hepatology. 2010 Jan;51(1):329-35
references.pmid: 19877180
references.citation: Reprod Biomed Online. 2005 Jan;10(1):105-10
references.pmid: 15705304
references.citation: Nat Methods. 2009 Nov;6(11):805-8
references.pmid: 19838168
references.citation: Cell Stem Cell. 2009 May 8;4(5):381-4
references.pmid: 19398399
references.citation: Br J Pharmacol. 2008 Aug;154(7):1379-81
references.pmid: 18536741
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6537-42
references.pmid: 21464322
references.citation: Science. 2008 Nov 7;322(5903):945-9
references.pmid: 18818365
references.citation: Nat Rev Drug Discov. 2007 Aug;6(8):605-16
references.pmid: 17667955
references.citation: Cell Metab. 2006 Oct;4(4):275-82
references.pmid: 17011500
references.citation: J Clin Invest. 2010 Sep;120(9):3127-36
references.pmid: 20739751
references.citation: Stem Cells. 2010 Oct;28(10):1893-904
references.pmid: 20715183
references.citation: Cell. 2011 Feb 4;144(3):439-52
references.pmid: 21295703
references.citation: Cell Death Differ. 2011 May;18(5):745-53
references.pmid: 21311564
references.citation: Hum Mol Genet. 2011 Aug 15;20(16):3176-87
references.pmid: 21593220
references.citation: Genes Dev. 2005 May 15;19(10):1129-55
references.pmid: 15905405
references.citation: Stem Cells. 2009 Mar;27(3):559-67
references.pmid: 19259936
references.citation: Hum Mol Genet. 2011 Sep 15;20(18):3642-52
references.pmid: 21685205
references.citation: Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):257-60
references.pmid: 17229967
references.citation: Cell Stem Cell. 2009 Oct 2;5(4):434-41
references.pmid: 19796623
references.citation: Mol Ther. 2010 Feb;18(2):386-93
references.pmid: 19997091
references.citation: Cell Stem Cell. 2011 Jul 8;9(1):17-23
references.pmid: 21726830
references.citation: Neurobiol Dis. 1996 Apr;3(2):97-110
references.pmid: 9173917
references.citation: Cell Stem Cell. 2010 Nov 5;7(5):618-30
references.pmid: 20888316
references.citation: Cell Stem Cell. 2011 Jun 3;8(6):688-94
references.pmid: 21596650
references.citation: FEBS Lett. 2009 Mar 18;583(6):1029-33
references.pmid: 19250937
references.citation: PLoS One. 2010 Dec 09;5(12):e15526
references.pmid: 21170306
references.citation: Am J Hum Genet. 2001 Mar;68(3):598-605
references.pmid: 11179008
references.citation: Mol Ther. 2011 Oct;19(10):1905-12
references.pmid: 21772256
references.citation: Science. 2008 Nov 7;322(5903):949-53
references.pmid: 18845712
references.citation: Nature. 2006 Nov 30;444(7119):532-3
references.pmid: 17136064
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: Nature. 2011 Mar 3;471(7336):58-62
references.pmid: 21368824
references.citation: Toxicol Sci. 2004 Jun;79(2):214-23
references.pmid: 15014205
references.citation: Aging (Albany NY). 2011 Apr;3(4):380-90
references.pmid: 21483033
references.citation: In Vitro Cell Dev Biol Anim. 2010 Apr;46(3-4):327-36
references.pmid: 20186514
references.citation: Nat Biotechnol. 2007 Jun;25(6):681-6
references.pmid: 17529971
references.citation: Arch Intern Med. 2005 Jun 27;165(12):1363-9
references.pmid: 15983284
references.citation: Nat Methods. 2011 May;8(5):409-12
references.pmid: 21460823
references.citation: Blood. 2011 May 26;117(21):5561-72
references.pmid: 21411759
references.citation: Cell Stem Cell. 2007 Sep 13;1(3):245-7
references.pmid: 18371358
references.citation: Nat Biotechnol. 2007 Feb;25(2):207-15
references.pmid: 17287758
references.citation: Stem Cells. 2010 Jan;28(1):64-74
references.pmid: 19904830
references.citation: Cell. 2008 Feb 22;132(4):661-80
references.pmid: 18295582
references.citation: Science. 2007 May 18;316(5827):1039-43
references.pmid: 17463250
references.citation: Stroke. 2008 Jun;39(6):1751-8
references.pmid: 18369171
references.citation: Cell Stem Cell. 2011 Jan 7;8(1):106-18
references.pmid: 21211785
references.citation: Cell. 2008 Sep 5;134(5):877-86
references.pmid: 18691744
references.citation: Nature. 2010 Sep 16;467(7313):285-90
references.pmid: 20644535
references.citation: Cell. 2010 Nov 12;143(4):527-39
references.pmid: 21074045
references.citation: Cell Stem Cell. 2011 Apr 8;8(4):376-88
references.pmid: 21474102
references.citation: Nature. 2011 May 12;473(7346):221-5
references.pmid: 21490598
references.citation: Nature. 2011 Apr 14;472(7342):221-5
references.pmid: 21346760
references.citation: Nat Methods. 2010 Mar;7(3):197-9
references.pmid: 20139967
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):11-4
references.pmid: 20621043
references.citation: Nature. 2009 Apr 9;458(7239):771-5
references.pmid: 19252477
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17967-72
references.pmid: 17098871
references.citation: PLoS One. 2011 Feb 10;6(2):e17084
references.pmid: 21347327
references.citation: Nat Biotechnol. 2010 Aug;28(8):848-55
references.pmid: 20644536
references.citation: Blood. 2010 Jul 22;116(3):386-95
references.pmid: 20439621
references.citation: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9222-7
references.pmid: 20442331
references.citation: Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(8):348-62
references.pmid: 19838014
references.citation: Nature. 2011 Mar 3;471(7336):63-7
references.pmid: 21368825
references.citation: Science. 2007 Dec 21;318(5858):1917-20
references.pmid: 18029452
references.citation: Hum Reprod. 2006 Feb;21(2):503-11
references.pmid: 16284066
references.citation: Nat Methods. 2009 May;6(5):370-6
references.pmid: 19404254
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):15-9
references.pmid: 20621044
references.citation: Tissue Eng Part A. 2010 Jul;16(7):2197-206
references.pmid: 20146561
references.citation: Clin Pharmacol Ther. 2008 Feb;83(2):227-30
references.pmid: 18202690
references.citation: Nature. 2009 Sep 3;461(7260):86-90
references.pmid: 19672241