Novel insights into disease modeling using induced pluripotent stem cells

Biological and Pharmaceutical Bulletin

Volumn 36, Issue 2, 2013, Pages 182-188

  Egashira, Toru ^a   Yuasa, Shinsuke ^a   Fukuda, Keiichi ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Cardiovascular disease; Disease modeling; Induced pluripotent stem cell; Long QT syndrome

Indexed keywords

ARTICLE; CARDIOVASCULAR DISEASE; CELL CHARACTERIZATION; CELL DERIVATION; CELL DIFFERENTIATION; CELL FUNCTION; CELL SPECIFICITY; CELLULAR PARAMETERS; DISEASE MODEL; DISEASE SELECTION; GENE MUTATION; GENERAL ASPECTS OF DISEASE; HEART MUSCLE CELL; HUMAN; LONG QT SYNDROME; PERSONALIZED MEDICINE; PLURIPOTENT STEM CELL;

ANIMALS; CARDIOVASCULAR DISEASES; GENETIC DISEASES, INBORN; HUMANS; INDIVIDUALIZED MEDICINE; INDUCED PLURIPOTENT STEM CELLS; MODELS, BIOLOGICAL;

EID: 84874023197     PISSN: 09186158     EISSN: 13475215     Source Type: Journal    
DOI: 10.1248/bpb.b12-00960     Document Type: Article

References (77)

1. Takahashi K, Tanabe K, Ohnuki M., Narita M, Ichisaka T, Tomoda K., Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861-872 (2007).
2. Yu J, Vodyanik MA, Smuga-Otto K, antosiewicz-Bourget J, Frane JL, Tian S, Nie J., Jonsdottir GA, Ruotti V, Stewart R, Slukvin I.I., Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917-1920 (2007).
3. Yu J, Hu K, Smuga-Otto K, Tian S., Stewart R, Slukvin II, Thomson JA Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324, 797-801 (2009).
4. Kim D, Kim C-H, Moon J-I, Chung YG, Chang M.Y., Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4, 472-476 (2009).
5. Ban H, Nishishita N, Fusaki N., Tabata T, Saeki K, Shikamura M., Takada N, Inoue M, Hasegawa M., Kawamata S, Nishikawa S. 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 (2011).
6. Warren L, Manos PD, Ahfeldt T, Loh Y.H., Li H., Lau F, Ebina W, Mandal P.K., Smith ZD, Meissner A, Daley GQ, Brack A.S., Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7, 618-630 (2010).
7. Miyoshi N, Ishii H, Nagano H., Haraguchi N, Dewi DL, Kano Y, Nishikawa S., Tanemura M, Mimori K, Tanaka F., Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. Reprogramming of mouse and human cells to pluripotency using mature microRNas. Cell Stem Cell, 8, 633-638 (2011).
8. Murry CE, Keller G. differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell, 132, 661-680 (2008).
9. Irion S, Nostro MC, Kattman S.J., Keller GM directed differentiation of pluripotent stem cells: from developmental biology to therapeutic applications. Cold Spring Harb. Symp. Quant. Biol., 73, 101-110 (2008).
10. Byrne Ja. Generation of isogenic pluripotent stem cells. Hum. Mol. Genet., 17 (R1), R37-R41 (2008).
11. Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457, 277-280 (2009).
12. Brennand KJ, Simone A, Jou J., Gelboin-Burkhart C, Tran N, Sangar S., Li Y, Mu Y, Chen G., Yu D, Mccarthy S, Sebat J, Gage FH. Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473, 221-225 (2011).
13. Egashira T, Yuasa S, Suzuki T., Aizawa Y, Yamakawa H, Matsuhashi T., Ohno Y, Tohyama S, Okata S., Seki T, Kuroda Y, Yae K, Hashimoto H, Tanaka T, Hattori F, Sato T, Miyoshi S, Takatsuki S, Murata M, Kurokawa J, Furukawa T, Makita N, Aiba T, Shimizu W, Horie M, Kamiya K, Kodama I, Ogawa S, Fukuda K. disease characterization using LQTS-specific induced pluripotent stem cells. Cardiovasc. Res., 95, 419-429 (2012).
14. Osafune K, Caron L, Borowiak M., Martinez RJ, Fitz-Gerald CS, Sato Y, Cowan C.A., Chien KR, Melton DA Marked differences in differentiation propensity among human embryonic stem cell lines. Nat. Biotechnol., 26, 313-315 (2008).
15. Dimos JT, Rodolfa KT, Niakan K.K., Weisenthal LM, Mitsumoto H, Chung W, Croft G.F., Saphier G., Leibel R, Goland R, Wichterle H., Henderson CE, Eggan K. Induced pluripotent stem cells generated from patients with aLS can be differentiated into motor neurons. Science, 321, 1218-1221 (2008).
16. Hochedlinger K, Plath K. Epigenetic reprogramming and induced pluripotency. Development, 136, 509-523 (2009).
17. Meissner A. Epigenetic modifications in pluripotent and differentiated cells. Nat. Biotechnol., 28, 1079-1088 (2010).
18. Tanaka T, Takahashi K, Yamane M., Tomida S, Nakamura S, Oshima K., Niwa A, Nishikomori R, Kambe N., Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Sato-Otsubo A, Ogawa S, Asaka I, Heike T, Yamanaka S, Nakahata T, Saito MK. Induced pluripotent stem cells from cINca syndrome patients as a model for dissecting somatic mosaicism and drug discovery. Blood, 120, 1299-1308 (2012).
19. Goldenberg I, Moss AJ Long QT syndrome. J. Am. Coll. Cardiol., 51, 2291-2300 (2008).
20. Marbán E. cardiac channelopathies. Nature, 415, 213-218 (2002).
21. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663-676 (2006).
22. Soldner F, Hockemeyer D, Beard C., Gao Q, Bell GW, Cook E.G., Hargus G., Blak A, Cooper O, Mitalipova M., Isacson O, Jaenisch R. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136, 964-977 (2009).
23. Seki T, Yuasa S, Oda M., Egashira T, Yae K, Kusumoto D., Nakata H, Tohyama S, Hashimoto H., Kodaira M, Okada Y, Seimiya H, Fusaki N, Hasegawa M, Fukuda K. Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell, 7, 11-14 (2010).
24. Maherali N, Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell, 3, 595-605 (2008).
25. Gore A, Li Z, Fung H-L, Young JE, Agarwal S, antosiewicz-Bourget J, Canto I., Giorgetti A, Israel MA, Kiskinis E, Lee J.H., Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature, 471, 63-67 (2011).
26. Laurent LC, Ulitsky I, Slavin I., Tran H, Schork A, Morey R., Lynch C, Harness JV, Lee S, Barrero M.J., Ku S., Martynova M, Semechkin R, Galat V, Gottesfeld J, Izpisua Belmonte JC, Murry C, Keirstead HS, Park HS, Schmidt U, Laslett AL, Muller FJ, Nievergelt CM, Shamir R, Loring JF. dynamic changes in the copy number of pluripotency and cell proliferation genes in human EScs and iPScs during reprogramming and time in culture. Cell Stem Cell, 8, 106-118 (2011).
27. Mekhoubad S, Bock C, de Boer AS, Kiskinis E, Meissner A, Eggan K. Erosion of dosage compensation impacts human iPSc disease modeling. Cell Stem Cell, 10, 595-609 (2012).
28. Ohi Y, Qin H, Hong C., Blouin L, Polo JM, Guo T, Qi Z., Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M., Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M. Incomplete dNa methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat. Cell Biol., 13, 541-549 (2011).
29. Soldner F, Laganière J, Cheng A.W., Hockemeyer D., Gao Q, Alagappan R, Khurana V., Golbe LI, Myers RH, Lindquist S, Zhang L., Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell, 146, 318-331 (2011).
30. Ananiev G, Williams EC, Li H, chang Q. 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 (2011).
31. Srivastava D. Making or breaking the heart: from lineage determination to morphogenesis. Cell, 126, 1037-1048 (2006).
32. Hu B-Y, Weick J.P., Yu J., Ma LX, Zhang XQ, Thomson JA, Zhang SC Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc. Natl. Acad. Sci. U.S.A., 107, 4335-4340 (2010).
33. Kattman SJ, Witty AD, Gagliardi M, Dubois N.C., Niapour M., Hotta A, Ellis J, Keller G. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell, 8, 228-240 (2011).
34. Polo JM, Liu S, Figueroa M.E., Kulalert W., Eminli S, Tan KY, Apostolou E, Stadtfeld M., Li Y, Shioda T, Natesan S., Wagers AJ, Melnick A, Evans T, Hochedlinger K. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat. Biotechnol., 28, 848-855 (2010).
35. Kim K, Doi A, Wen B., Ng K, Zhao R, Cahan P., Kim J, Aryee MJ, Ji H, Ehrlich L.I., Yabuuchi A., Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ. Epigenetic memory in induced pluripotent stem cells. Nature, 467, 285-290 (2010).
36. Kim K, Zhao R, Doi A., Ng K, Unternaehrer J, Cahan P., Huo H, Loh YH, Aryee M.J., Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat. Biotechnol., 29, 1117-1119 (2011).
37. Hattori F, Chen H, Yamashita H., Tohyama S, Satoh YS, Yuasa S, Li W., Yamakawa H, Tanaka T, Onitsuka T., Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K. Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat. Methods, 7, 61-66 (2010).
38. Dubois NC, Craft AM, Sharma P, Elliott D.A., Stanley EG, Elefanty AG, Gramolini A, Keller G. SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat. Biotechnol., 29, 1011-1018 (2011).
39. Nelson TJ, Martinez-Fernandez A, Terzic A. Induced pluripotent stem cells: developmental biology to regenerative medicine. Nat. Rev. Cardiol., 7, 700-710 (2010).
40. Blazeski A, Zhu R, Hunter D.W., Weinberg SH, Zambidis ET, Tung L. cardiomyocytes derived from human induced pluripotent stem cells as models for normal and diseased cardiac electrophysiology and contractility. Prog. Biophys. Mol. Biol., 110, 166-177 (2012).
41. Szabo E, Rampalli S, Risueño RM, Schnerch A., Mitchell R, Fiebig-Comyn A, Levadoux-Martin M, Bhatia M. direct conversion of human fibroblasts to multilineage blood progenitors. Nature, 468, 521-526 (2010).
42. Ambasudhan R, Talantova M, Coleman R., Yuan X, Zhu S, Lipton S.A., Ding S. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell, 9, 113-118 (2011).
43. Qiang L, Fujita R, Yamashita T., Angulo S, Rhinn H, Rhee D., Doege C, Chau L, Aubry L., Vanti WB, Moreno H, Abeliovich A. Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons. Cell, 146, 359-371 (2011).
44. Koch P, Tamboli IY, Mertens J, Wunderlich P., Ladewig J, Stüber K, Esselmann H., Wiltfang J, Brüstle O, Walter J. Presenilin-1 L166P mutant human pluripotent stem cell-derived neurons exhibit partial loss of γ-secretase activity in endogenous amyloid-β generation. Am. J. Pathol., 180, 2404-2416 (2012).
45. Nguyen HN, Byers B, Cord B., Shcheglovitov A, Byrne J, Gujar P., Kee K, Schüle B, Dolmetsch R.E., Langston W., Palmer TD, Pera RR. LRRK2 mutant iPSc-derived da neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell, 8, 267-280 (2011).
46. Itzhaki I, Maizels L, Huber I., Gepstein A, Arbel G, Caspi O., Miller L, Belhassen B, Nof E., Glikson M, Gepstein L. Modeling of catecholaminergic polymorphic ventricular tachycardia with patient-specific human-induced pluripotent stem cells. J. Am. Coll. Cardiol., 60, 990-1000 (2012).
47. Sun N, Yazawa M, Liu J., Han L, Sanchez-Freire V, Abilez OJ, Navarrete E.G., Hu S., Wang L, Lee A, Pavlovic A., Lin S, Chen R, Hajjar RJ, Snyder MP, Dolmetsch RE, Butte MJ, Ashley EA, Longaker MT, Robbins RC, Wu JC. Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci. Transl. Med., 4, ra47 (2012).
48. Rashid ST, Corbineau S, Hannan N., Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J., Ahrlund-Richter L, Skepper J, Semple R., Weber A, Lomas DA, Vallier L. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Invest., 120, 3127-3136 (2010).
49. Kumano K, Arai S, Hosoi M., Taoka K, Takayama N, Otsu M., Nagae G, Ueda K, Nakazaki K., Kamikubo Y, Eto K, Aburatani H, Nakauchi H, Kurokawa M. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood, 119, 6234-6242 (2012).
50. Fujikura J, Nakao K, Sone M., Noguchi M, Mori E, Naito M., Taura D, Harada-Shiba M, Kishimoto I, Watanabe A., Asaka I, Hosoda K, Nakao K. Induced pluripotent stem cells generated from diabetic patients with mitochondrial dNa a3243G mutation. Diabetologia, 55, 1689-1698 (2012).
51. Shi Y, Kirwan P, Smith J., MacLean G, Orkin SH, Livesey FJ a human stem cell model of early alzheimer's disease pathology in down syndrome. Sci. Transl. Med., 4, ra29 (2012).
52. Batista LFZ, Pech MF, Zhong F.L., Nguyen HN, Xie KT, Zaug AJ, Crary S.M., Choi J., Sebastiano V, Cherry A, Giri N., Wernig M, Alter BP, Cech TR, Savage SA, Reijo Pera RA, Artandi SE. Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature, 474, 399-402 (2011).
53. Agarwal S, Loh Y-H, McLoughlin EM, Huang J, Park I.H., Miller JD, Huo H, Okuka M, dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature, 464, 292-296 (2010).
54. Jin Z-B, Okamoto S., Osakada F, Homma K, Assawachananont J., Hirami Y, Iwata T, Takahashi M. Modeling retinal degeneration using patient-specific induced pluripotent stem cells. PLoS ONE, 6, e17084 (2011).
55. Mazzulli JR, Xu Y-H, Sun Y, Knight A.L., McLean PJ, Caldwell GA, Sidransky E, Grabowski G.A., Krainc D. Gaucher disease glucocere-brosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell, 146, 37-52 (2011).
56. Israel MA, Yuan SH, Bardy C, Reyna S.M., Mu Y., Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo F.S., Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, Goldstein LS. Probing sporadic and familial alzheimer's disease using induced pluripotent stem cells. Nature, 482, 216-220 (2012).
57. cohen JD, Babiarz JE, Abrams R.M., Guo L., Kameoka S, Chiao E, Taunton J., Kolaja KL use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations. Toxicol. Appl. Pharmacol., 257, 74-83 (2011).
58. Tanaka T, Tohyama S, Murata M., Nomura F, Kaneko T, Chen H., Hattori F, Egashira T, Seki T., Ohno Y, Koshimizu U, Yuasa S, Ogawa S, Yamanaka S, Yasuda K, Fukuda K. in vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem. Biophys. Res. Commun., 385, 497-502 (2009).
59. Zhang J, Wilson GF, Soerens A.G., Koonce CH, Yu J, Palecek SP, Thomson J.A., Kamp TJ Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res., 104, e30-e41 (2009).
60. Germanguz I, Sedan O, Zeevi-Levin N, Shtrichman R., Barak E, Ziskind A, Eliyahu S., Meiry G, Amit M, Itskovitz-Eldor J, Binah O. Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells. J. Cell. Mol. Med., 15, 38-51 (2011).
61. Zeevi-Levin N., Itskovitz-Eldor J, Binah O. cardiomyocytes derived from human pluripotent stem cells for drug screening. Pharmacol. Ther., 134, 180-188 (2012).
62. Moretti A, Bellin M, Welling A., Jung CB, Lam JT, Bott-Flügel L, Dorn T, Goedel A, Höhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schömig A, Laugwitz KL. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N. Engl. J. Med., 363, 1397-1409 (2010).
63. Itzhaki I, Maizels L, Huber I., Zwi-Dantsis L, Caspi O, Winterstern A., Feldman O, Gepstein A, Arbel G., Hammerman H, Boulos M, Gepstein L. Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471, 225-229 (2011).
64. Matsa E, Rajamohan D, Dick E., Young L, Mellor I, Staniforth A., Denning C. drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. Eur. Heart J., 32, 952-962 (2011).
65. Yazawa M, Hsueh B, Jia X., Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature, 471, 230-234 (2011).
66. Davis RP, Casini S, van den Berg CW, Hoekstra M, Remme CA, Dambrot C, Salvatori D, Oostwaard DW, Wilde AA, Bezzina CR, Verkerk AO, Freund C, Mummery CL. cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation, 125, 3079-3091 (2012).
67. Lahti AL, Kujala VJ, Chapman H, Koivisto A P, Pekkanen-Mattila M, Kerkelä E, Hyttinen J, Kontula K, Swan H, Conklin BR, Yamanaka S, Silvennoinen O, Aalto-Setälä K. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis. Model Mech., 5, 220-230 (2012).
68. Chouabe C, Neyroud N, Richard P., Denjoy I, Hainque B, Romey G., Drici MD, Guicheney P, Barhanin J. Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk. Cardiovasc. Res., 45, 971-980 (2000).
69. Zipes DP, Camm AJ, Borggrefe M, Buxton A.E., Chaitman B., Fromer M, Gregoratos G, Klein G., Moss AJ, Myerburg RJ, Priori SG, Quinones M.A., Roden DM, Silka MJ, Tracy C, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Blanc JJ, Budaj A, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano J Lamerican college of cardiology/american Heart association Task Force, European Society of cardiology committee for Practice Guidelines, European Heart Rhythm association, Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation, 114, e385-e484 (2006).
70. Vyas H, Hejlik J, Ackerman MJ Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation, 113, 1385-1392 (2006).
71. Shimizu W, Noda T, Takaki H., Nagaya N, Satomi K, Kurita T., Suyama K, Aihara N, Sunagawa K., Echigo S, Miyamoto Y, Yoshimasa Y, Nakamura K, Ohe T, Towbin JA, Priori SG, Kamakura S. diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm, 1, 276-283 (2004).
72. Napolitano C, Priori SG, Schwartz P.J., Bloise R., Ronchetti E, Nastoli J, Bottelli G., Cerrone M, Leonardi S. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA, 294, 2975-2980 (2005).
73. Hescheler J, Halbach M, Egert U., Lu ZJ, Bohlen H, Fleischmann BK, Reppel M. determination of electrical properties of ES cell-derived cardiomyocytes using MEas. J. Electrocardiol., 37 (Suppl.), 110-116 (2004).
74. Roden DM, Abraham RL Refining repolarization reserve. Heart Rhythm, 8, 1756-1757 (2011).
75. Roden DM. clinical practice. Long-QT syndrome. N. Engl. J. Med., 358, 169-176 (2008).
76. Fitzgerald PT, Ackerman MJ drug-induced torsades de pointes: the evolving role of pharmacogenetics. Heart Rhythm, 2 (Suppl.), S30-S37 (2005).
77. Prescott C. The business of exploiting induced pluripotent stem cells. Philos. Trans. R. Soc. Lond. B Biol. Sci., 366, 2323-2328 (2011).