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iPSC technology-Powerful hand for disease modeling and therapeutic screen
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  • Journal title : BMB Reports
  • Volume 48, Issue 5,  2015, pp.256-265
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.5.100
 Title & Authors
iPSC technology-Powerful hand for disease modeling and therapeutic screen
Kim, Changsung;
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Cardiovascular and neurodegenerative diseases are major health threats in many developed countries. Recently, target tissues derived from human embryonic stem (hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes (CMs) or neurons, have been actively mobilized for drug screening. Knowledge of drug toxicity and efficacy obtained using stem cell-derived tissues could parallel that obtained from human trials. Furthermore, iPSC disease models could be advantageous in the development of personalized medicine in various parts of disease sectors. To obtain the maximum benefit from iPSCs in disease modeling, researchers are now focusing on aging, maturation, and metabolism to recapitulate the pathological features seen in patients. Compared to pediatric disease modeling, adult-onset disease modeling with iPSCs requires proper maturation for full manifestation of pathological features. Herein, the success of iPSC technology, focusing on patient-specific drug treatment, maturation-based disease modeling, and alternative approaches to compensate for the current limitations of patient iPSC modeling, will be further discussed. [BMB Reports 2015; 48(5): 256-265]
Disease modeling;Drug screen;IPSC;Patient specific therapy;Stem cell;
 Cited by
Hematopoietic stem cell expansion and generation: the ways to make a breakthrough,Park, Bokyung;Yoo, Keon Hee;Kim, Changsung;

BLOOD RESEARCH, 2015. vol.50. 4, pp.194-203 crossref(new window)
MicroRNA-mediated maturation of human pluripotent stem cell-derived cardiomyocytes: Towards a better model for cardiotoxicity?, Food and Chemical Toxicology, 2016  crossref(new windwow)
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Rajamohan D, Matsa E, Kalra S et al (2013) Current status of drug screening and disease modelling in human pluripotent stem cells. Bioessays 35, 281-298 crossref(new window)

Rubin LL and Haston KM (2011) Stem cell biology and drug discovery. BMC Biol 9, 42 crossref(new window)

Seok J, Warren HS, Cuenca AG et al (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110, 3507-3512 crossref(new window)

Munos B (2009) Lessons from 60 years of pharmaceutical innovation. Nat Rev Drug Discov 8, 959-968 crossref(new window)

Park IH, Arora N, Huo H et al (2008) Disease-specific induced pluripotent stem cells. Cell 134, 877-886 crossref(new window)

Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 crossref(new window)

Takahashi K and Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 crossref(new window)

Ban H, Nishishita N, Fusaki N et al (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108, 14234-14239 crossref(new window)

Kim C (2014) Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application. Blood Res 49, 7-14 crossref(new window)

Mercola M, Ruiz-Lozano P, Schneider MD (2011) Cardiac muscle regeneration: lessons from development. Genes Dev 25, 299-309 crossref(new window)

Nascone N and Mercola M (1995) An inductive role for the endoderm in Xenopus cardiogenesis. Development 121, 515-523

Kim C, Majdi M, Xia P et al (2010) Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation. Stem Cells Dev 19, 783-795 crossref(new window)

Filipczyk AA, Passier R, Rochat A et al (2007) Regulation of cardiomyocyte differentiation of embryonic stem cells by extracellular signalling. Cell Mol Life Sci 64, 704-718 crossref(new window)

Yang L, Soonpaa MH, Adler ED et al (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453, 524-528 crossref(new window)

Lian X, Hsiao C, Wilson G et al (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109, E1848-1857 crossref(new window)

Moretti A, Bellin M, Welling A et al (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363, 1397-1409 crossref(new window)

Itzhaki I, Maizels L, Huber I et al (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471, 225-229 crossref(new window)

Yazawa M, Hsueh B, Jia X et al (2011) Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471, 230-234 crossref(new window)

Ruan Y, Liu N, Napolitano C and Priori SG (2008) Therapeutic strategies for long-QT syndrome: does the molecular substrate matter? Circ Arrhythm Electrophysiol 1, 290-297 crossref(new window)

Terrenoire C, Wang K, Tung KW et al (2013) Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics. J Gen Physiol 141, 61-72 crossref(new window)

Moreno JD and Clancy CE (2012) Pathophysiology of the cardiac late Na current and its potential as a drug target. J Mol Cell Cardiol 52, 608-619 crossref(new window)

Carvajal-Vergara X, Sevilla A, D'Souza SL et al (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465, 808-812 crossref(new window)

Lan F, Lee AS, Liang P et al (2013) Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell 12, 101-113 crossref(new window)

Tabar V and Studer L (2014) Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet 15, 82-92 crossref(new window)

Zhang SC, Wernig M, Duncan ID, Brüstle O and Thomson JA (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 19, 1129-1133 crossref(new window)

Reubinoff BE, Itsykson P, Turetsky T et al (2001) Neural progenitors from human embryonic stem cells. Nat Biotechnol 19, 1134-1140 crossref(new window)

Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M and Studer L. (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27, 275-280 crossref(new window)

Kondo T, Asai M, Tsukita K et al (2013) Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12, 487-496 crossref(new window)

Yagi T, Ito D, Okada Y et al (2011) Modeling familial Alzheimer's disease with induced pluripotent stem cells. Hum Mol Genet 20, 4530-4539 crossref(new window)

Wang H and Doering LC (2012) Induced pluripotent stem cells to model and treat neurogenetic disorders. Neural Plast 2012, 346053

Israel MA, Yuan SH, Bardy C et al (2012) Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 482, 216-220

Brennand KJ, Simone A, Jou J et al (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221-225 crossref(new window)

Ryan SD, Dolatabadi N, Chan SF et al (2013) Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1alpha transcription. Cell 155, 1351-1364 crossref(new window)

Kaye JA and Finkbeiner S (2013) Modeling Huntington's disease with induced pluripotent stem cells. Mol Cell Neurosci 56, 50-64 crossref(new window)

Jeon I, Lee N, Li JY et al (2012) Neuronal properties, in vivo effects, and pathology of a Huntington's disease patient-derived induced pluripotent stem cells. Stem Cells 30, 2054-2062 crossref(new window)

Zhang K, Yi F, Liu GH and Izpisua Belmonte JC (2012) Huntington's disease: dancing in a dish. Cell Res 22, 1627-1630 crossref(new window)

Williams EC, Zhong X, Mohamed A et al (2014) Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum Mol Genet 23, 2968-2980 crossref(new window)

Jeon I, Choi C, Lee N et al (2014) In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC) in the YAC128 Model of Huntington's Disease. Int J Stem Cells 7, 43-47 crossref(new window)

Yang J, Cai J, Zhang Y et al (2010) Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome. J Biol Chem 285, 40303-40311 crossref(new window)

Dajani R, Koo SE, Sullivan GJ and Park IH (2013) Investigation of Rett syndrome using pluripotent stem cells. J Cell Biochem 114, 2446-2453 crossref(new window)

Ananiev G, Williams EC, Li H and Chang Q (2011) Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from Rett syndrome patients as in vitro disease model. PLoS One 6, e25255 crossref(new window)

Schöndorf DC, Aureli M, McAllister FE et al (2014) iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis. Nat Commun 5, 4028

Chamberlain SJ, Chen PF, Ng KY et al (2010) Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A 107, 17668-17673 crossref(new window)

Sareen D, Ebert AD, Heins BM, McGivern JV, Ornelas L and Svendsen CN (2012) Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One 7, e39113 crossref(new window)

Egawa N and Inoue H (2013) [ALS disease modeling and drug screening using patient-specific iPS cells]. Rinsho Shinkeigaku 53, 1020-1022 crossref(new window)

Corti S, Nizzardo M, Simone C et al (2012) Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med 4, 165ra162 crossref(new window)

Ross CA and Akimov SS (2014) Human-induced pluripotent stem cells: potential for neurodegenerative diseases. Hum Mol Genet 23, R17-26 crossref(new window)

Kiskinis E, Sandoe J, Williams LA et al (2014) Pathways Disrupted in Human ALS Motor Neurons Identified through Genetic Correction of Mutant SOD1. Cell Stem Cell 14, 781-795 crossref(new window)

Chen H, Qian K, Du Z et al (2014) Modeling ALS with iPSCs Reveals that Mutant SOD1 Misregulates Neurofilament Balance in Motor Neurons. Cell Stem Cell 14, 796-809 crossref(new window)

Wolstencroft EC, Mattis V, Bajer AA, Young PJ and Lorson CL (2005) A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels. Hum Mol Genet 14, 1199-1210 crossref(new window)

Makhortova NR, Hayhurst M and Cerqueira A (2011) A screen for regulators of survival of motor neuron protein levels. Nat Chem Biol 7, 544-552 crossref(new window)

Guo X, Disatnik MH, Monbureau M, Shamloo M, Mochly -Rosen D and Qi X (2013) Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration. J Clin Invest 123, 5371-5388 crossref(new window)

Charbord J, Poydenot P, Bonnefond C et al (2013) High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes. Stem Cells 31, 1816-1828 crossref(new window)

Miller JD, Ganat YM, Kishinevsky S et al (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13, 691-705 crossref(new window)

Kim C, Wong J, Wen J et al (2013) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature 494, 105-110 crossref(new window)

Reinhardt P, Schmid B, Burbulla LF et al (2013) Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12, 354-367 crossref(new window)

Lopaschuk GD and Jaswal JS (2010) Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. J Cardiovasc Pharmacol 56, 130-140 crossref(new window)

Djouadi F, Lecarpentier Y, Hébert JL, Charron P, Bastin J and Coirault C (2009) A potential link between peroxisome proliferator-activated receptor signalling and the pathogenesis of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Res 84, 83-90 crossref(new window)

Eroshenko N, Ramachandran R, Yadavalli VK and Rao RR (2013) Effect of substrate stiffness on early human embryonic stem cell differentiation. J Biol Eng 7, 7 crossref(new window)

Engler AJ, Carag-Krieger C, Johnson CP et al (2008) Embryonic cardiomyocytes beat best on a matrix with heartlike elasticity: scar-like rigidity inhibits beating. J Cell Sci 121, 3794-3802 crossref(new window)

Galie PA, Khalid N, Carnahan KE, Westfall MV and Stegemann JP (2013) Substrate stiffness affects sarcomere and costamere structure and electrophysiological function of isolated adult cardiomyocytes. Cardiovasc Pathol 22, 219-227 crossref(new window)

Choi SM, Kim Y, Shim JS et al (2013) Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57, 2458-2468 crossref(new window)

Hidvegi T, Ewing M, Hale P et al (2010) An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science 329, 229-232 crossref(new window)

Höing S, Rudhard Y, Reinhardt P et al (2012) Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay. Cell Stem Cell 11, 620-632 crossref(new window)

Yang YM, Gupta SK, Kim KJ et al (2013) A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell 12, 713-726 crossref(new window)

Fermini B and Fossa AA (2003) The impact of drug-induced QT interval prolongation on drug discovery and development. Nat Rev Drug Discov 2, 439-447 crossref(new window)

Zeevi-Levin N, Itskovitz-Eldor J and Binah O (2012) Cardiomyocytes derived from human pluripotent stem cells for drug screening. Pharmacol Ther 134, 180-188 crossref(new window)

De Bruin ML, Pettersson M, Meyboom RH, Hoes AW and Leufkens HG (2005) Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 26, 590-597 crossref(new window)

Liang P, Lan F, Lee AS et al (2013) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127, 1677-1691 crossref(new window)

Grant AO (2009) Cardiac ion channels. Circ Arrhythm Electrophysiol 2, 185-194 crossref(new window)

Knollmann BC (2013) Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model? Circ Res 112, 969-976; discussion 976 crossref(new window)

Musunuru K (2013) Genome editing of human pluripotent stem cells to generate human cellular disease models. Dis Model Mech 6, 896-904 crossref(new window)

Kim H and Kim JS (2014) A guide to genome engineering with programmable nucleases. Nat Rev Genet 15, 321-334 crossref(new window)

Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH and Joung JK (2013) CRISPR RNA-guided activation of endogenous human genes. Nat Methods 10, 977-979 crossref(new window)

Qiang L, Fujita R and Abeliovich A (2013) Remodeling neurodegeneration: somatic cell reprogramming-based models of adult neurological disorders. Neuron 78, 957-969 crossref(new window)

Wada R, Muraoka N, Inagawa K et al (2013) Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci U S A 110, 12667-12672 crossref(new window)

Fu JD, Stone NR, Liu L et al (2013) Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State. Stem Cell Reports 1, 235-247 crossref(new window)

Cerrone M, Lin X, Zhang M et al (2014) Missense mutations in plakophilin-2 cause sodium current deficit and associate with a brugada syndrome phenotype. Circulation 129, 1092-1103 crossref(new window)