title: Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges.
abstract: Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an 'in vivo' platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the 'ideal' neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced.
authors.affiliation: National Neuroscience Institute, Singapore, Singapore.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Huck Hui
authors.initials: HH
authors.lastname: Ng
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: National Neuroscience Institute, Singapore, Singapore Genome Institute of Singapore, Singapore, Singapore Department of Neurology, Singapore General Hospital, Singapore, Singapore Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use; D002454:Cell Differentiation / Q000502:physiology; D059290:Dopaminergic Neurons / Q000166:cytology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D010300:Parkinson Disease / Q000628:therapy*
chemical_list: D000978:Antiparkinson Agents
keywords: PARKINSON'S DISEASE
references.citation: Arch Neurol. 2010 Jun;67(6):670-6
references.pmid: 20558386
references.citation: J Parkinsons Dis. 2011;1(4):395-412
references.pmid: 23933658
references.citation: Nature. 2011 Mar 3;471(7336):63-7
references.pmid: 21368825
references.citation: Nature. 2015 Jun 18;522(7556):340-4
references.pmid: 26061766
references.citation: Lancet. 2014 Aug 9;384(9942):545-55
references.pmid: 24954676
references.citation: EMBO Mol Med. 2012 May;4(5):380-95
references.pmid: 22407749
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12175-80
references.pmid: 17586681
references.citation: Sci Transl Med. 2010 Jun 30;2(38):38ra46
references.pmid: 20592420
references.citation: Nat Med. 2008 May;14(5):501-3
references.pmid: 18391963
references.citation: Circ Res. 2013 Feb 1;112(3):523-33
references.pmid: 23371901
references.citation: Nat Genet. 2014 Sep;46(9):989-93
references.pmid: 25064009
references.citation: J Clin Invest. 2012 Aug;122(8):2928-39
references.pmid: 22751106
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):267-80
references.pmid: 21362567
references.citation: Stem Cells. 2009 May;27(5):1050-6
references.pmid: 19415771
references.citation: Cell. 2013 Dec 5;155(6):1351-64
references.pmid: 24290359
references.citation: Nat Commun. 2011 Aug 23;2:440
references.pmid: 21863007
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Nat Genet. 2006 Apr;38(4):431-40
references.pmid: 16518401
references.citation: Nat Med. 2008 May;14(5):504-6
references.pmid: 18391962
references.citation: Hum Mol Genet. 2011 Mar 1;20(5):927-40
references.pmid: 21147754
references.citation: J Clin Invest. 2011 Feb;121(2):715-25
references.pmid: 21245577
references.citation: J Neurochem. 2009 Nov;111(3):696-702
references.pmid: 19694908
references.citation: Curr Biol. 2012 Mar 20;22(6):545-52
references.pmid: 22342752
references.citation: Stem Cells Transl Med. 2014 May;3(5):586-98
references.pmid: 24646489
references.citation: J Neurosci. 2011 Apr 20;31(16):5970-6
references.pmid: 21508222
references.citation: Ann Neurol. 2004 Jun;55(6):896; author reply 896-7
references.pmid: 15174028
references.citation: Cell Stem Cell. 2013 Oct 3;13(4):382-4
references.pmid: 24094319
references.citation: Stem Cells. 2013 Aug;31(8):1548-62
references.pmid: 23666606
references.citation: Cell Stem Cell. 2013 Dec 5;13(6):691-705
references.pmid: 24315443
references.citation: J Clin Invest. 2011 Jun;121(6):2326-35
references.pmid: 21576821
references.citation: Sci Transl Med. 2012 Jul 4;4(141):141ra90
references.pmid: 22764206
references.citation: Nat Biotechnol. 2008 Nov;26(11):1276-84
references.pmid: 18931654
references.citation: Stem Cell Reports. 2014 Mar 06;2(3):337-50
references.pmid: 24672756
references.citation: Nature. 2009 Aug 27;460(7259):1149-53
references.pmid: 19668189
references.citation: J Biol Chem. 2013 Jan 25;288(4):2223-37
references.pmid: 23212910
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5856-61
references.pmid: 18391196
references.citation: N Engl J Med. 2001 Mar 8;344(10):710-9
references.pmid: 11236774
references.citation: Nature. 2011 Nov 06;480(7378):547-51
references.pmid: 22056989
references.citation: Science. 2015 Aug 7;349(6248):1255555
references.pmid: 26250687
references.citation: Neurology. 2014 Jul 29;83(5):406-12
references.pmid: 24975862