High throughput physiological screening of iPSC-derived cardiomyocytes for drug development

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1863, Issue 7, 2016, Pages 1717-1727

  del Álamo, Juan C ^a   Lemons, Derek ^b,c   Serrano, Ricardo ^a   Savchenko, Alex ^b,c,e   Cerignoli, Fabio ^d   Bodmer, Rolf ^c   Mercola, Mark ^b,c,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c BURNHAM INSTITUTE   (United States)

^d ACEA Biosciences Inc   (United States)

^e STANFORD UNIVERSITY   (United States)

Author keywords

Automated microscopy; Cardiomyocyte; Drug discovery; Heart; High content screening; Particle image velocimetry; Physiology

Indexed keywords

ARTICLE; CARDIAC MUSCLE CELL; CARDIOTOXICITY; CELL FUNCTION; GENETIC DISORDER; HEART ARRHYTHMIA; HEART MUSCLE CONTRACTILITY; HIGH THROUGHPUT SCREENING; HUMAN; INDUCED PLURIPOTENT STEM CELL; METABOLIC DISORDER; PRIORITY JOURNAL; RISK ASSESSMENT; ANIMAL; CELL CULTURE; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CHEMICALLY INDUCED; DRUG DEVELOPMENT; DRUG EFFECTS; GENETIC PREDISPOSITION; GENETICS; HEART CONTRACTION; HEART DISEASES; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PROCEDURES;

CARDIOVASCULAR AGENT;

ANIMALS; CARDIOVASCULAR AGENTS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CELLS, CULTURED; DRUG DISCOVERY; GENETIC PREDISPOSITION TO DISEASE; HEART DISEASES; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MYOCARDIAL CONTRACTION; MYOCYTES, CARDIAC; PHENOTYPE; RISK ASSESSMENT;

EID: 84962082104     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2016.03.003     Document Type: Article

References (136)

1. Balinsky B.I. Experiments on total extirpation of the whole endoderm in Triton embryos. C.r. Acad. Sci. URSS 1939, 23:196-198.
2. Chuang H.H., Tseng M.P. An experimental analysis of the determination and differentiation of the mesodermal structures of neurula in urodeles. Sci. Sinica 1957, 6:669-708.
3. Jacobson A.G. Influences of ectoderm and endoderm on heart differentiation in the newt. Dev. Biol. 1960, 2:138-154.
4. Jacobson A.G. Heart determination in the newt. J. Exp. Zool. 1961, 146:139-152.
5. Nieuwkoop P.D. Experimental investigations on the origin and determination of the germ cells, and on the development of the lateral plates and germ ridges in Urodeles. Arch. Néerl. Zool. 1947, 8:1-205.
6. Sater A.K., Jacobson A.G. The specification of heart mesoderm occurs during gastrulation in Xenopus laevis. Development 1989, 105:821-830.
7. Nascone N., Mercola M. An inductive role for the endoderm in Xenopus cardiogenesis. Development 1995, 121:515-523.
8. Sater A.K., Jacobson A.G. The role of the dorsal lip in the induction of heart mesoderm in Xenopus laevis. Development 1990, 108:461-470.
9. Orts-Llorca F. Influence of the endoderm on heart differentiation during the early stages of development of the chicken embryo. Wilhelm Roux Arch. EntwMech. Org. 1963, 154:533-551.
10. Orts-Llorca F., Gil D.R. Influence of the endoderm on heart differentiation. Wilhelm Roux ARch. EntwMech. Org. 1965, 156:368-370.
11. Schultheiss T.M., Xydas S., Lassar A.B. Induction of avian cardiac myogenesis by anterior endoderm. Development 1995, 121:4203-4214.
12. Schneider V.A., Mercola M. Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev. 2001, 15:304-315.
13. Marvin M.J., Di Rocco G., Gardiner A., Bush S.M., Lassar A.B. Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev. 2001, 15:316-327.
14. Meganathan K., Sotiriadou I., Natarajan K., Hescheler J., Sachinidis A. Signaling molecules, transcription growth factors and other regulators revealed from in-vivo and in-vitro models for the regulation of cardiac development. Int. J. Cardiol. 2015, 183:117-128.
15. Willems E., Spiering S., Davidovics H., Lanier M., Xia Z., Dawson M., Cashman J., Mercola M. Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circ. Res. 2011, 109:360-364.
16. Kattman S.J., Witty A.D., 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 2011, 8:228-240.
17. Zhu W.Z., Van Biber B., Laflamme M.A. Methods for the derivation and use of cardiomyocytes from human pluripotent stem cells. Methods Mol. Biol. 2011, 767:419-431.
18. Lian X., Zhang J., Azarin S.M., Zhu K., Hazeltine L.B., Bao X., Hsiao C., Kamp T.J., Palecek S.P. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/beta-catenin signaling under fully defined conditions. Nat. Protoc. 2013, 8:162-175.
19. Burridge P.W., Keller G., Gold J.D., Wu J.C. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 2012, 10:16-28.
20. Ma J., Guo L., Fiene S.J., Anson B.D., Thomson J.A., Kamp T.J., Kolaja K.L., Swanson B.J., January C.T. High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. Am. J. Physiol. Heart Circ. Physiol. 2011, 301:H2006-H2017.
21. Hoekstra M., Mummery C.L., Wilde A.A., Bezzina C.R., Verkerk A.O. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias. Front. Physiol. 2012, 3:346.
22. Knollmann B.C. Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model?. Circ. Res. 2013, 112:969-976. discussion 976.
23. Keung W., Boheler K.R., Li R.A. Developmental cues for the maturation of metabolic, electrophysiological and calcium handling properties of human pluripotent stem cell-derived cardiomyocytes. Stem Cell Res. Ther. 2014, 5:17.
24. Kim C., Majdi M., Xia P., Wei K.A., Talantova M., Spiering S., Nelson B., Mercola M., Chen H.S. Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation. Stem Cells Dev. 2010, 19:783-795.
25. Pekkanen-Mattila M., Ojala M., Kerkela E., Rajala K., Skottman H., Aalto-Setala K. The effect of human and mouse fibroblast feeder cells on cardiac differentiation of human pluripotent stem cells. Stem Cells Int. 2012, 2012:875059.
26. Zhang Q., Jiang J., Han P., Yuan Q., Zhang J., Zhang X., Xu Y., Cao H., Meng Q., Chen L., Tian T., Wang X., Li P., Hescheler J., Ji G., Ma Y. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals. Cell Res. 2011, 21:579-587.
27. Lundy S.D., Zhu W.Z., Regnier M., Laflamme M.A. Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev. 2013, 22:1991-2002.
28. Ibrahim M., Gorelik J., Yacoub M.H., Terracciano C.M. The structure and function of cardiac t-tubules in health and disease. Proc. Biol. Sci. 2011, 278:2714-2723.
29. Dolnikov K., Shilkrut M., Zeevi-Levin N., Gerecht-Nir S., Amit M., Danon A., Itskovitz-Eldor J., Binah O. Functional properties of human embryonic stem cell-derived cardiomyocytes: intracellular Ca2+ handling and the role of sarcoplasmic reticulum in the contraction. Stem Cells 2006, 24:236-245.
30. Poon E., Kong C.W., Li R.A. Human pluripotent stem cell-based approaches for myocardial repair: from the electrophysiological perspective. Mol. Pharm. 2011, 8:1495-1504.
31. Nikolaev V.O., Bunemann M., Schmitteckert E., Lohse M.J., Engelhardt S. Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching beta1-adrenergic but locally confined beta2-adrenergic receptor-mediated signaling. Circ. Res. 2006, 99:1084-1091.
32. Perry S.J., Baillie G.S., Kohout T.A., McPhee I., Magiera M.M., Ang K.L., Miller W.E., McLean A.J., Conti M., Houslay M.D., Lefkowitz R.J. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science 2002, 298:834-836.
33. Jung G., Fajardo G., Ribeiro A.J.S., Kooiker K.B., Coronado M., Zhao M., Hu D.-Q., Reddy S., Kodo K., Sriram K., Insel P.A., Wu J.C., Pruitt B.L., Bernstein D. Time-dependent evolution of functional vs. remodeling signaling in ipsc-derived cardiomyocytes and induced maturation with biomechanical stimulation. FASEB J. 2015, (in press).
34. Lyon A.R., MacLeod K.T., Zhang Y., Garcia E., Kanda G.K., Lab M.J., Korchev Y.E., Harding S.E., Gorelik J. Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:6854-6859.
35. Nikolaev V.O., Moshkov A., Lyon A.R., Miragoli M., Novak P., Paur H., Lohse M.J., Korchev Y.E., Harding S.E., Gorelik J. Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 2010, 327:1653-1657.
36. Kaumann A., Bartel S., Molenaar P., Sanders L., Burrell K., Vetter D., Hempel P., Karczewski P., Krause E.G. Activation of beta2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure. Circulation 1999, 99:65-72.
37. Lefkowitz R.J. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J. Biol. Chem. 1998, 273:18677-18680.
38. Rapacciuolo A., Suvarna S., Barki-Harrington L., Luttrell L.M., Cong M., Lefkowitz R.J., Rockman H.A. Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways. J. Biol. Chem. 2003, 278:35403-35411.
39. Ojamaa K., Klemperer J.D., MacGilvray S.S., Klein I., Samarel A. Thyroid hormone and hemodynamic regulation of beta-myosin heavy chain promoter in the heart. Endocrinology 1996, 137:802-808.
40. Lee J., Yun M.J., Nam K.H., Chung W.Y., Soh E.Y., Park C.S. Quality of life and effectiveness comparisons of thyroxine withdrawal, triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone administration for low-dose radioiodine remnant ablation of differentiated thyroid carcinoma. Thyroid 2010, 20:173-179.
41. Fu J.D., Rushing S.N., Lieu D.K., Chan C.W., Kong C.W., Geng L., Wilson K.D., Chiamvimonvat N., Boheler K.R., Wu J.C., Keller G., Hajjar R.J., Li R.A. Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PLoS One 2011, 6.
42. Parker K.K., Tan J., Chen C.S., Tung L. Myofibrillar architecture in engineered cardiac myocytes. Circ. Res. 2008, 103:340-342.
43. Sun Y., Jallerat Q., Szymanski J.M., Feinberg A.W. Conformal nanopatterning of extracellular matrix proteins onto topographically complex surfaces. Nat. Methods 2015, 12:134-136.
44. Kim J., Park J., Na K., Yang S., Baek J., Yoon E., Choi S., Lee S., Chun K., Park J., Park S. Quantitative evaluation of cardiomyocyte contractility in a 3D microenvironment. J. Biomech. 2008, 41:2396-2401.
45. Kim D.H., Lipke E.A., Kim P., Cheong R., Thompson S., Delannoy M., Suh K.Y., Tung L., Levchenko A. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:565-570.
46. Ribeiro A.J., Ang Y.S., Fu J.D., Rivas R.N., Mohamed T.M., Higgs G.C., Srivastava D., Pruitt B.L. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc. Natl. Acad. Sci. U. S. A. 2015, 112:12705-12710.
47. Hirt M.N., Hansen A., Eschenhagen T. Cardiac tissue engineering: state of the art. Circ. Res. 2014, 114:354-367.
48. Thavandiran N., Dubois N., Mikryukov A., Masse S., Beca B., Simmons C.A., Deshpande V.S., McGarry J.P., Chen C.S., Nanthakumar K., Keller G.M., Radisic M., Zandstra P.W. Design and formulation of functional pluripotent stem cell-derived cardiac microtissues. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:E4698-E4707.
49. Miller J.S., Stevens K.R., Yang M.T., Baker B.M., Nguyen D.H., Cohen D.M., Toro E., Chen A.A., Galie P.A., Yu X., Chaturvedi R., Bhatia S.N., Chen C.S. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 2012, 11:768-774.
50. Morgan J.P., Delnero P.F., Zheng Y., Verbridge S.S., Chen J., Craven M., Choi N.W., Diaz-Santana A., Kermani P., Hempstead B., Lopez J.A., Corso T.N., Fischbach C., Stroock A.D. Formation of microvascular networks in vitro. Nat. Protoc. 2013, 8:1820-1836.
51. Sekine H., Shimizu T., Sakaguchi K., Dobashi I., Wada M., Yamato M., Kobayashi E., Umezu M., Okano T. In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat. Commun. 2013, 4:1399.
52. Wyrsch P., Blenn C., Pesch T., Beneke S., Althaus F.R. Cytosolic Ca2+ shifts as early markers of cytotoxicity. Cell Commun. Signal 2013, 11:11.
53. Spencer C.I., Baba S., Nakamura K., Hua E.A., Sears M.A., Fu C.C., Zhang J., Balijepalli S., Tomoda K., Hayashi Y., Lizarraga P., Wojciak J., Scheinman M.M., Aalto-Setala K., Makielski J.C., January C.T., Healy K.E., Kamp T.J., Yamanaka S., Conklin B.R. Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia. Stem Cell Rep. 2014, 3:269-281.
54. Grienberger C., Konnerth A. Imaging calcium in neurons. Neuron 2012, 73:862-885.
55. Sirenko O., Crittenden C., Callamaras N., Hesley J., Chen Y.W., Funes C., Rusyn I., Anson B., Cromwell E.F. Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using iPSC cells. J. Biomol. Screen. 2013, 18:39-53.
56. Molokanova E., Savchenko A. Bright future of optical assays for ion channel drug discovery. Drug Discov. Today 2008, 13:14-22.
57. Grimm F.A., Iwata Y., Sirenko O., Bittner M., Rusyn I. High-content assay multiplexing for toxicity screening in induced pluripotent stem cell-derived cardiomyocytes and hepatocytes. Assay Drug Dev. Technol. 2015, 13:529-546.
58. Fluhler E., Burnham V.G., Loew L.M. Spectra, membrane binding, and potentiometric responses of new charge shift probes. Biochemistry 1985, 24:5749-5755.
59. Loew L.M. Potentiometric dyes: imaging electrical activity of cell membranes. Pure Appl. Chem. 2009, 68:1405-1409.
60. Lopez-Izquierdo A., Warren M., Riedel M., Cho S., Lai S., Lux R.L., Spitzer K.W., Benjamin I.J., Tristani-Firouzi M., Jou C.J. A near-infrared fluorescent voltage-sensitive dye allows for moderate-throughput electrophysiological analyses of human induced pluripotent stem cell-derived cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 2014, 307:H1370-H1377.
61. Bradley J., Luo R., Otis T.S., DiGregorio D.A. Submillisecond optical reporting of membrane potential in situ using a neuronal tracer dye. J. Neurosci. 2009, 29:9197-9209.
62. Miller E.W., Lin J.Y., Frady E.P., Steinbach P.A., Kristan W.B., Tsien R.Y. Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:2114-2119.
63. Black H.S. Modulation Theory 1953, Van Nostrand, (Place Published).
64. Siegel M.S., Isacoff E.Y. A genetically encoded optical probe of membrane voltage. Neuron 1997, 19:735-741.
65. Chang Liao M.L., de Boer T.P., Mutoh H., Raad N., Richter C., Wagner E., Downie B.R., Unsold B., Arooj I., Streckfuss-Bomeke K., Doker S., Luther S., Guan K., Wagner S., Lehnart S.E., Maier L.S., Stuhmer W., Wettwer E., van Veen T., Morlock M.M., Knopfel T., Zimmermann W.H. Sensing cardiac electrical activity with a cardiac myocyte-targeted optogenetic voltage indicator. Circ. Res. 2015, 117:401-412.
66. Jin L., Han Z., Platisa J., Wooltorton J.R., Cohen L.B., Pieribone V.A. Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe. Neuron 2012, 75:779-785.
67. Shinnawi R., Huber I., Maizels L., Shaheen N., Gepstein A., Arbel G., Tijsen A.J., Gepstein L. Monitoring human-induced pluripotent stem cell-derived cardiomyocytes with genetically encoded calcium and voltage fluorescent reporters. Stem Cell Rep. 2015, 5:582-596.
68. Leyton-Mange J.S., Mills R.W., Macri V.S., Jang M.Y., Butte F.N., Ellinor P.T., Milan D.J. Rapid cellular phenotyping of human pluripotent stem cell-derived cardiomyocytes using a genetically encoded fluorescent voltage sensor. Stem Cell Rep. 2014, 2:163-170.
69. St-Pierre F., Marshall J.D., Yang Y., Gong Y., Schnitzer M.J., Lin M.Z. High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor. Nat. Neurosci. 2014, 17:884-889.
70. Piao H.H., Rajakumar D., Kang B.E., Kim E.H., Baker B.J. Combinatorial mutagenesis of the voltage-sensing domain enables the optical resolution of action potentials firing at 60 Hz by a genetically encoded fluorescent sensor of membrane potential. J. Neurosci. 2015, 35:372-385.
71. Halbach M.D., Egert U., Hescheler J., Banach K. Estimation of action potential changes from field potential recordings in multicellular mouse cardiac myocyte cultures. Cell. Physiol. Biochem. 2003, 13:271-284.
72. Guo L., Qian J.Y., Abrams R., Tang H.M., Weiser T., Sanders M.J., Kolaja K.L. The electrophysiological effects of cardiac glycosides in human iPSC-derived cardiomyocytes and in guinea pig isolated hearts. Cell. Physiol. Biochem. 2011, 27:453-462.
73. Harris K., Aylott M., Cui Y., Louttit J.B., McMahon N.C., Sridhar A. Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays. Toxicol. Sci. 2013, 134:412-426.
74. Navarrete E.G., Liang P., Lan F., Sanchez-Freire V., Simmons C., Gong T., Sharma A., Burridge P.W., Patlolla B., Lee A.S., Wu H., Beygui R.E., Wu S.M., Robbins R.C., Bers D.M., Wu J.C. Screening drug-induced arrhythmia using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation 2013, 128:S3-S13.
75. Bornholz B., Weidtkamp-Peters S., Schmitmeier S., Seidel C.A., Herda L.R., Felix S.B., Lemoine H., Hescheler J., Nguemo F., Schafer C., Christensen M.O., Mielke C., Boege F. Impact of human autoantibodies on beta1-adrenergic receptor conformation, activity, and internalization. Cardiovasc. Res. 2013, 97:472-480.
76. Eldridge S., Guo L., Mussio J., Furniss M., Hamre J., Davis M. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Sci. 2014, 141:547-559.
77. Abassi Y.A., Xi B., Li N., Ouyang W., Seiler A., Watzele M., Kettenhofen R., Bohlen H., Ehlich A., Kolossov E., Wang X., Xu X. Dynamic monitoring of beating periodicity of stem cell-derived cardiomyocytes as a predictive tool for preclinical safety assessment. Br. J. Pharmacol. 2012, 165:1424-1441.
78. Xi B., Wang T., Li N., Ouyang W., Zhang W., Wu J., Xu X., Wang X., Abassi Y.A. Functional cardiotoxicity profiling and screening using the xCELLigence RTCA cardio system. J. Assoc. Lab. Autom. 2011, 16:415-421.
79. Guo L., Abrams R.M.C., Babiarz J.E., Cohen J.D., Kameoka S., Sanders M.J., Chiao E., Kolaja K.L. Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Sci. 2011, 123:281-289.
80. Scott C.W., Zhang X., Abi-Gerges N., Lamore S.D., Abassi Y.A., Peters M.F. An impedance-based cellular assay using human iPSC-derived cardiomyocytes to quantify modulators of cardiac contractility. Toxicol. Sci. 2014, 142:331-338.
81. Guo L., Eldridge S., Furniss M., Mussio J., Davis M. Use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to monitor compound effects on cardiac myocyte signaling pathways. Curr. Protoc. Chem. Biol. 2015, 7:141-185.
82. Feinberg A.W., Feigel A., Shevkoplyas S.S., Sheehy S., Whitesides G.M., Parker K.K. Muscular thin films for building actuators and powering devices. Science 2007, 317:1366-1370.
83. Grosberg A., Nesmith A.P., Goss J.A., Brigham M.D., McCain M.L., Parker K.K. Muscle on a chip: in vitro contractility assays for smooth and striated muscle. J. Pharmacol. Toxicol. Methods 2012, 65:126-135.
84. Sheehy S.P., Pasqualini F., Grosberg A., Park S.J., Aratyn-Schaus Y., Parker K.K. Quality metrics for stem cell-derived cardiac myocytes. Stem Cell Rep. 2014, 2:282-294.
85. Banerjee I., Carrion K., Serrano R., Dyo J., Sasik R., Lund S., Willems E., Aceves S., Meili R., Mercola M., Chen J., Zambon A., Hardiman G., Doherty T.A., Lange S., del Alamo J.C., Nigam V. Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-beta signaling. J. Mol. Cell. Cardiol. 2015, 79:133-144.
86. Jacot J.G., McCulloch A.D., Omens J.H. Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. Biophys. J. 2008, (in revision).
87. del Alamo J.C., Meili R., Alvarez-Gonzalez B., Alonso-Latorre B., Bastounis E., Firtel R., Lasheras J.C. Three-dimensional quantification of cellular traction forces and mechanosensing of thin substrata by fourier traction force microscopy. PLoS One 2013, 8.
88. Del Alamo J.C., Meili R., Alonso-Latorre B., Rodriguez-Rodriguez J., Aliseda A., Firtel R.A., Lasheras J.C. Spatio-temporal analysis of eukaryotic cell motility by improved force cytometry. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:13343-13348.
89. Hur S.S., del Alamo J.C., Park J.S., Li Y.S., Nguyen H.A., Teng D., Wang K.C., Flores L., Alonso-Latorre B., Lasheras J.C., Chien S. Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:11110-11115.
90. Tambe D.T., Croutelle U., Trepat X., Park C.Y., Kim J.H., Millet E., Butler J.P., Fredberg J.J. Monolayer stress microscopy: limitations, artifacts, and accuracy of recovered intercellular stresses. PLoS One 2013, 8.
91. Lee E.K., Kurokawa Y.K., Tu R., George S.C., Khine M. Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs. Sci. Rep. 2015, 5:11817.
92. Huebsch N., Loskill P., Mandegar M.A., Marks N.C., Sheehan A.S., Ma Z., Mathur A., Nguyen T.N., Yoo J.C., Judge L.M., Spencer C.I., Chukka A.C., Russell C.R., So P.L., Conklin B.R., Healy K.E. Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial Scales. Tissue Eng. Part C Methods 2015, 21:467-479.
93. Maddah M., Heidmann J.D., Mandegar M.A., Walker C.D., Bolouki S., Conklin B.R., Loewke K.E. A non-invasive platform for functional characterization of stem-cell-derived cardiomyocytes with applications in cardiotoxicity testing. Stem Cell Rep. 2015, 4:621-631.
94. Adrian R.J., Westerweel J. Particle Image Velocimetry 2001, Cambridge University Press, Place Published.
95. Priori S.G., Napolitano C., Di Pasquale E., Condorelli G. Induced pluripotent stem cell-derived cardiomyocytes in studies of inherited arrhythmias. J. Clin. Invest. 2013, 123:84-91.
96. Kim C., Wong J., Wen J., Wang S., Wang C., Spiering S., Kan N.G., Forcales S., Puri P.L., Leone T.C., Marine J.E., Calkins H., Kelly D.P., Judge D.P., Chen H.S. Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature 2013, 494:105-110.
97. Ma D., Wei H., Lu J., Ho S., Zhang G., Sun X., Oh Y., Tan S.H., Ng M.L., Shim W., Wong P., Liew R. Generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes as a cellular model of arrhythmogenic right ventricular cardiomyopathy. Eur. Heart J. 2013, 34:1122-1133.
98. Rajamohan D., Matsa E., Kalra S., Crutchley J., Patel A., George V., Denning C. Current status of drug screening and disease modelling in human pluripotent stem cells. BioEssays 2013, 35:281-298.
99. Mercola M., Colas A., Willems E. Induced pluripotent stem cells in cardiovascular drug discovery. Circ. Res. 2013, 112:534-548.
100. Dell'Era P., Benzoni P., Crescini E., Valle M., Xia E., Consiglio A., Memo M. Cardiac disease modeling using induced pluripotent stem cell-derived human cardiomyocytes. World J. Stem Cells 2015, 7:329-342.
101. Lopaschuk G.D., Folmes C.D., Stanley W.C. Cardiac energy metabolism in obesity. Circ. Res. 2007, 101:335-347.
102. Peura J.L., Scheffer J.E. Lipotoxicity in the cardiac and skeletal muscle. Heart Metab. 2006, 30:4-6.
103. Heather L.C., Clarke K. Metabolism, hypoxia and the diabetic heart. J. Mol. Cell. Cardiol. 2011, 50:598-605.
104. Zimmet P., Alberti K.G., Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001, 414:782-787.
105. Nakamura K., Hirano K., Wu S.M. iPS cell modeling of cardiometabolic diseases. J. Cardiovasc. Transl. Res. 2013, 6:46-53.
106. Schweiger M., Lass A., Zimmermann R., Eichmann T.O., Zechner R. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am. J. Physiol. Endocrinol. Metab. 2009, 297:E289-E296.
107. Roden D.M. Clinical practice. Long-QT syndrome. N. Engl. J. Med. 2008, 358:169-176.
108. Waring M.J., Arrowsmith J., Leach A.R., Leeson P.D., Mandrell S., Owen R.M., Pairaudeau G., Pennie W.D., Pickett S.D., Wang J., Wallace O., Weir A. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov. 2015, 14:475-486.
109. Mullard A. New drugs cost US[dollar]2.6 billion to develop. Nat. Rev. Drug Discov. 2014, 13:877.
110. M. Herper, The truly staggering cost of inventing new drugs, Forbes (online), (2012). http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/.
111. Sager P.T., Gintant G., Turner J.R., Pettit S., Stockbridge N. Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the Cardiac Safety Research Consortium. Am. Heart J. 2014, 167:292-300.
112. Lawrence C.L., Pollard C.E., Hammond T.G., Valentin J.P. Nonclinical proarrhythmia models: predicting Torsades de Pointes. J. Pharmacol. Toxicol. Methods 2005, 52:46-59.
113. Kannankeril P., Roden D.M., Darbar D. Drug-induced long QT syndrome. Pharmacol. Rev. 2010, 62:760-781.
114. Yang T., Snyders D., Roden D.M. Drug block of I(kr): model systems and relevance to human arrhythmias. J. Cardiovasc. Pharmacol. 2001, 38:737-744.
115. Aiba T., Shimizu W., Inagaki M., Noda T., Miyoshi S., Ding W.G., Zankov D.P., Toyoda F., Matsuura H., Horie M., Sunagawa K. Cellular and ionic mechanism for drug-induced long QT syndrome and effectiveness of verapamil. J. Am. Coll. Cardiol. 2005, 45:300-307.
116. Wu L., Shryock J.C., Song Y., Belardinelli L. An increase in late sodium current potentiates the proarrhythmic activities of low-risk QT-prolonging drugs in female rabbit hearts. J. Pharmacol. Exp. Ther. 2006, 316:718-726.
117. Roden D.M., Yang T. Protecting the heart against arrhythmias: potassium current physiology and repolarization reserve. Circulation 2005, 112:1376-1378.
118. May J.E., Xu J., Morse H.R., Avent N.D., Donaldson C. Toxicity testing: the search for an in vitro alternative to animal testing. Br. J. Biomed. Sci. 2009, 66:160-165.
119. Price P.S., Keenan R.E., Swartout J.C. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans. Toxicol. Appl. Pharmacol. 2008, 233:64-70.
120. Sugiyama A. Sensitive and reliable proarrhythmia in vivo animal models for predicting drug-induced torsades de pointes in patients with remodelled hearts. Br. J. Pharmacol. 2008, 154:1528-1537.
121. Townsend C., Brown B.S. Predicting drug-induced QT prolongation and torsades de pointes: a review of preclinical endpoint measures. Curr. Protoc. Pharmacol. 2013, 10. Unit 10 16, Chapter.
122. Qian J.-Y., Guo L. Altered cytosolic Ca2+ dynamics in cultured Guinea pig cardiomyocytes as an in vitro model to identify potential cardiotoxicants. Toxicol. in Vitro 2010, 24:960-972.
123. Wohlfart B. Analysis of mechanical alternans in rabbit papillary muscle. Acta Physiol. Scand. 1982, 115:405-414.
124. Verrier R.L., Klingenheben T., Malik M., El-Sherif N., Exner D.V., Hohnloser S.H., Ikeda T., Martinez J.P., Narayan S.M., Nieminen T., Rosenbaum D.S. Microvolt T-wave alternans physiological basis, methods of measurement, and clinical utility-consensus guideline by International Society for Holter and Noninvasive Electrocardiology. J. Am. Coll. Cardiol. 2011, 58:1309-1324.
125. Verrier R.L., Malik M. Quantitative T-wave alternans analysis for guiding medical therapy: an underexploited opportunity. Trends Cardiovasc. Med. 2015, 25:201-213.
126. Kanaporis G., Blatter L.A. The mechanisms of calcium cycling and action potential dynamics in cardiac alternans. Circ. Res. 2015, 116:846-856.
127. Sharma A., Burridge P.W., McKeithan W.L., Serrano R., Holmström A., Churko J.M., Matsa E., Zhang Y., Kumar A., Álamo J.C.d., Mercola M., Wu S.M., Wu J.C. High-Throughput Screening of Tyrosine Kinase Inhibitors in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals a Class-Specific Cardiotoxicity Pattern 2016, (submitted).
128. Chaudhari U., Nemade H., Wagh V., Gaspar J.A., Ellis J.K., Srinivasan S.P., Spitkovski D., Nguemo F., Louisse J., Bremer S., Hescheler J., Keun H.C., Hengstler J.G., Sachinidis A. Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch. Toxicol. 2015.
129. Ewer M.S., Ewer S.M. Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol. 2015, 12:620.
130. Hahn V.S., Lenihan D.J., Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J. Am. Heart Assoc. 2014, 3.
131. Gaspar J.A., Doss M.X., Hengstler J.G., Cadenas C., Hescheler J., Sachinidis A. Unique metabolic features of stem cells, cardiomyocytes, and their progenitors. Circ. Res. 2014, 114:1346-1360.
132. Liang P., Lan F., Lee A.S., Gong T., Sanchez-Freire V., Wang Y., Diecke S., Sallam K., Knowles J.W., Wang P.J., Nguyen P.K., Bers D.M., Robbins R.C., Wu J.C. Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 2013, 127:1677-1691.
133. Hwang P.M., Sykes B.D. Targeting the sarcomere to correct muscle function. Nat. Rev. Drug Discov. 2015, 14:313-328.
134. Mathur A., Loskill P., Shao K., Huebsch N., Hong S., Marcus S.G., Marks N., Mandegar M., Conklin B.R., Lee L.P., Healy K.E. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 2015, 5:8883.
135. Reddy S., Bernstein D. Molecular mechanisms of right ventricular failure. Circulation 2015, 132:1734-1742.
136. Feinstein J.A., Benson D.W., Dubin A.M., Cohen M.S., Maxey D.M., Mahle W.T., Pahl E., Villafane J., Bhatt A.B., Peng L.F., Johnson B.A., Marsden A.L., Daniels C.J., Rudd N.A., Caldarone C.A., Mussatto K.A., Morales D.L., Ivy D.D., Gaynor J.W., Tweddell J.S., Deal B.J., Furck A.K., Rosenthal G.L., Ohye R.G., Ghanayem N.S., Cheatham J.P., Tworetzky W., Martin G.R. Hypoplastic left heart syndrome: current considerations and expectations. J. Am. Coll. Cardiol. 2012, 59:S1-42.