Generic placeholder image

Current Pharmaceutical Biotechnology


ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Review Article

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

Author(s): Gil Bub and Matthew J. Daniels*

Volume 21, Issue 9, 2020

Page: [752 - 764] Pages: 13

DOI: 10.2174/1389201020666190405182251

open access plus


In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.

Keywords: Optogenetics, channelrhodopsin, halorhodopsin, archearhodospin, iPS-cardiomyocyte, cardiac, drug screening, re-entrant arrhythmia.

Graphical Abstract
Dunlop, J.; Bowlby, M.; Peri, R.; Vasilyev, D.; Arias, R. High throughput electrophysiology: an emerging paradigm for ion channel screening and physiology. Nat. Rev. Drug Discov., 2008, 7(4), 358-368.
[] [PMID: 18356919]
Finkel, A.; Wittel, A.; Yang, N.; Handran, S.; Hughes, J.; Costantin, J. Population patch clamp improves data consistency and success rates in the measurement of ionic currents. J. Biomol. Screen., 2006, 11(5), 488-496.
[] [PMID: 16760372]
Li, T.; Lu, G.; Chiang, E.Y.; Chernov-Rogan, T.; Grogan, J.L.; Chen, J. High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE. PLoS One, 2017, 12(7) e0180154
[] [PMID: 28683073]
Stett, A.; Egert, U.; Guenther, E.; Hofmann, F.; Meyer, T.; Nisch, W.; Haemmerle, H. Biological application of microelectrode arrays in drug discovery and basic research. Anal. Bioanal. Chem., 2003, 377(3), 486-495.
[] [PMID: 12923608]
Clements, M.; Thomas, N. High-throughput multi-parameter profiling of electrophysiological drug effects in human embryonic stem cell derived cardiomyocytes using multi-electrode arrays. Toxicol. Sci., 2014, 140(2), 445-461.
[] [PMID: 24812011]
Spira, M.E.; Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotechnol., 2013, 8(2), 83-94.
[] [PMID: 23380931]
Zemelman, B.V.; Lee, G.A.; Ng, M.; Miesenböck, G. Selective photostimulation of genetically chARGed neurons. Neuron, 2002, 33(1), 15-22.
[] [PMID: 11779476]
Boyden, E.S.; Zhang, F.; Bamberg, E.; Nagel, G.; Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci., 2005, 8(9), 1263-1268.
[] [PMID: 16116447]
Arrenberg, A.B.; Stainier, D.Y.R.; Baier, H.; Huisken, J. Optogenetic control of cardiac function. Science, 2010, 330(6006), 971-974.
Bruegmann, T.; Malan, D.; Hesse, M.; Beiert, T.; Fuegemann, C.J.; Fleischmann, B.K.; Sasse, P. Optogenetic control of heart muscle in vitro and in vivo. Nat. Methods, 2010, 7(11), 897-900.
[] [PMID: 20881965]
Entcheva, E.; Bub, G. All-optical control of cardiac excitation: Combined high-resolution optogenetic actuation and optical mapping. J. Physiol., 2016, 594(9), 2503-2510.
[] [PMID: 26857427]
Broyles, C.N.; Robinson, P.; Daniels, M.J. Fluorescent, bioluminescent, and optogenetic approaches to study excitable physiology in the single cardiomyocyte. Cells, 2018, 7(6), 51.
[] [PMID: 29857560]
Jenkins, M.W.; Duke, A.R.; Gu, S.; Chiel, H.J.; Fujioka, H.; Watanabe, M.; Jansen, E.D.; Rollins, A.M.; Rollins, A.M. Optical pacing of the embryonic heart. Nat. Photonics, 2010, 4(9), 623-626.
[] [PMID: 21423854]
Jenkins, M.W.; Wang, Y.T.; Doughman, Y.Q.; Watanabe, M.; Cheng, Y.; Rollins, A.M. Optical pacing of the adult rabbit heart. Biomed. Opt. Express, 2013, 4(9), 1626-1635.
[] [PMID: 24049683]
Smith, N.I.; Kumamoto, Y.; Iwanaga, S.; Ando, J.; Fujita, K.; Kawata, S. A femtosecond laser pacemaker for heart muscle cells. Opt. Express, 2008, 16(12), 8604-8616.
[] [PMID: 18545573]
Grynkiewicz, G.; Poenie, M.; Tsien, R.Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 1985, 260(6), 3440-3450.
[PMID: 3838314]
Hwang, S-M.; Kim, T.Y.; Lee, K.J. Complex-periodic spiral waves in confluent cardiac cell cultures induced by localized inhomogeneities. Proc. Natl. Acad. Sci. USA, 2005, 102(29), 10363-10368.
[] [PMID: 15985555]
Burton, R.A.B.; Klimas, A.; Ambrosi, C.M.; Tomek, J.; Corbett, A.; Entcheva, E.; Bub, G. Optical control of excitation waves in cardiac tissue. Nat. Photonics, 2015, 9(12), 813-816.
[] [PMID: 27057206]
Christoph, J.; Chebbok, M.; Richter, C.; Schröder-Schetelig, J.; Bittihn, P.; Stein, S.; Uzelac, I.; Fenton, F.H.; Hasenfuß, G.; Gilmour, R.F., Jr; Luther, S. Electromechanical vortex filaments during cardiac fibrillation. Nature, 2018, 555(7698), 667-672.
[] [PMID: 29466325]
Nash, M.P.; Panfilov, A.V. Electromechanical model of excitable tissue to study reentrant cardiac arrhythmias. Prog. Biophys. Mol. Biol., 2004, 85(2-3), 501-522.
[] [PMID: 15142759]
Bishop, M.J.; Rowley, A.; Rodriguez, B.; Plank, G.; Gavaghan, D.J.; Bub, G. The role of photon scattering in voltage-calcium fluorescent recordings of ventricular fibrillation. Biophys. J., 2011, 101(2), 307-318.
[] [PMID: 21767482]
Hortigon-Vinagre, M.P.; Zamora, V.; Burton, F.L.; Green, J.; Gintant, G.A.; Smith, G.L. The use of ratiometric fluorescence measurements of the voltage sensitive dye Di-4-ANEPPS to Examine Action potential characteristics and drug effects on human induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Sci., 2016, 154(2), 320-331.
[] [PMID: 27621282]
Hecht, V.; Ferrante, J.; Atwater, N.; Werley, K.; McManus, O.; Urban, L.; Dempsey, G. Characterization of herg channel modulators in optically paced human ipsc-derived cardiomyocytes using ultra-wide field optopatch. J. Pharmacol. Toxicol. Methods, 2017, 88, 238.
Kralj, J.M.; Douglass, A.D.; Hochbaum, D.R.; Maclaurin, D.; Cohen, A.E. Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nat. Methods, 2011, 9(1), 90-95.
[] [PMID: 22120467]
Klimas, A.; Ambrosi, C.M.; Yu, J.; Williams, J.C.; Bien, H.; Entcheva, E.; Ambrosi, C.M.; Williams, J.C.; Bien, H.; Entcheva, E. OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology. Nat. Commun., 2016, 7, 11542.
[] [PMID: 27161419]
Agus, V.; Picardi, P.; Redaelli, L.; Scarabottolo, L.; Lohmer, S. Three-dimensional control of ion channel function through optogenetics and co-culture SLAS Discov. Adv. Life Sci. R.D., 2018, 23(1), 102-108.
Kettenhofen, R. HTS-Compatible Voltage- and Ca2+-Sensitive Dye Recordings from hiPSC-Derived Cardiomyocytes Using the Hamamatsu FDSS Systems; Humana Press: New York, NY, 2017, pp. 135-152.
Clements, I. P.; Millard, D. C.; Nicolini, A. M.; Preyer, A. J.; Grier, R.; Heckerling, A.; Blum, R. A.; Tyler, P.; McSweeney, K. M.; Lu, Y.-F.; Hall, D.; Ross, J. D. Optogenetic stimulation of multiwell MEA plates for neural and cardiac applications 2016, 9690, 96902.
Rehnelt, S.; Malan, D.; Juhasz, K.; Wolters, B.; Doerr, L.; Beckler, M.; Kettenhofen, R.; Bohlen, H.; Bruegmann, T.; Sasse, P. Frequency-dependent multi-well cardiotoxicity screening enabled by optogenetic stimulation. Int. J. Mol. Sci., 2017, 18(12), 2634.
[] [PMID: 29211031]
Lu, H.R.; Whittaker, R.; Price, J.H.; Vega, R.; Pfeiffer, E.R.; Cerignoli, F.; Towart, R.; Gallacher, D.J. high throughput measurement of ca++ dynamics in human stem cell-derived cardiomyocytes by kinetic image cytometery: a cardiac risk assessment characterization using a large panel of cardioactive and inactive compounds. Toxicol. Sci., 2015, 148(2), 503-516.
[] [PMID: 26358003]
Crocini, C.; Ferrantini, C.; Coppini, R.; Scardigli, M.; Yan, P.; Loew, L.M.; Smith, G.; Cerbai, E.; Poggesi, C.; Pavone, F.S.; Sacconi, L. Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation. Sci. Rep., 2016, 6, 35628.
[] [PMID: 27748433]
Scardigli, M.; Müllenbroich, C.; Margoni, E.; Cannazzaro, S.; Crocini, C.; Ferrantini, C.; Coppini, R.; Yan, P.; Loew, L.M.; Campione, M.; Bocchi, L.; Giulietti, D.; Cerbai, E.; Poggesi, C.; Bub, G.; Pavone, F.S.; Sacconi, L. Real-time optical manipulation of cardiac conduction in intact hearts. J. Physiol., 2018, 596(17), 3841-3858.
[] [PMID: 29989169]
Yu, J.; Chen, K.; Lucero, R.V.; Ambrosi, C.M.; Entcheva, E. Cardiac optogenetics: Enhancement by all-trans-retinal. Sci. Rep., 2015, 5, 16542.
[] [PMID: 26568132]
Wietek, J.; Prigge, M. “Enhancing channelrhodopsins: an overview,” in Optogenetics; Humana Press: New York, NY, 2016, pp. 141-165.
Mattis, J.; Tye, K.M.; Ferenczi, E.A.; Ramakrishnan, C.; O’Shea, D.J.; Prakash, R.; Gunaydin, L.A.; Hyun, M.; Fenno, L.E.; Gradinaru, V.; Yizhar, O.; Deisseroth, K. Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat. Methods, 2011, 9(2), 159-172.
[] [PMID: 22179551]
Chang, Y-F.; Broyles, C.N.; Brook, F.A.; Davies, M.J.; Turtle, C.W.; Nagai, T.; Daniels, M.J. Non-invasive phenotyping and drug testing in single cardiomyocytes or beta-cells by calcium imaging and optogenetics. PLoS One, 2017, 12(4) e0174181
[] [PMID: 28379974]
Govorunova, E.G.; Cunha, S.R.; Sineshchekov, O.A.; Spudich, J.L. Anion channelrhodopsins for inhibitory cardiac optogenetics. Sci. Rep., 2016, 6(1), 33530.
[] [PMID: 27628215]
Vogt, C.C.; Bruegmann, T.; Malan, D.; Ottersbach, A.; Roell, W.; Fleischmann, B.K.; Sasse, P. Systemic gene transfer enables optogenetic pacing of mouse hearts. Cardiovasc. Res., 2015, 106(2), 338-343.
[] [PMID: 25587047]
Bingen, B.O.; Engels, M.C.; Schalij, M.J.; Jangsangthong, W.; Neshati, Z.; Feola, I.; Ypey, D.L.; Askar, S.F.A.; Panfilov, A.V.; Pijnappels, D.A.; de Vries, A.A.F. Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes. Cardiovasc. Res., 2014, 104(1), 194-205.
[] [PMID: 25082848]
Majumder, R.; Feola, I.; Teplenin, A.S.; de Vries, A.A.F.; Panfilov, A.V.; Pijnappels, D.A. Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system. eLife, 2018, 7(e005591) e41076
[] [PMID: 30260316]
Feola, I.; Volkers, L.; Majumder, R.; Teplenin, A.; Schalij, M.J.; Panfilov, A.V.; de Vries, A.A.F.; Pijnappels, D.A. Localized optogenetic targeting of rotors in atrial cardiomyocyte monolayers. Circ. Arrhythm. Electrophysiol., 2017, 10(11) e006130
[] [PMID: 29097406]
Björk, S.; Ojala, E.A.; Nordström, T.; Ahola, A.; Liljeström, M.; Hyttinen, J.; Kankuri, E.; Mervaala, E. evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes. Front. Physiol., 2017, 8, 884.
[] [PMID: 29163220]
Yu, J.; Entcheva, E. Inscribing Optical Excitability to Non-Excitable Cardiac Cells: Viral Delivery of Optogenetic Tools in Primary Cardiac Fibroblasts; Methods in Molecular Biology; Springer New York, 2016, pp. 303-317.
Dempsey, G.T.; Chaudhary, K.W.; Atwater, N.; Nguyen, C.; Brown, B.S.; McNeish, J.D.; Cohen, A.E.; Kralj, J.M. Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging. J. Pharmacol. Toxicol. Methods, 2016, 81, 240-250.
[] [PMID: 27184445]
Ambrosi, C.M.; Boyle, P.M.; Chen, K.; Trayanova, N.A.; Entcheva, E. Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability. Sci. Rep., 2015, 5, 17350.
[] [PMID: 26621212]
Ambrosi, C.M.; Entcheva, E. Optogenetic control of cardiomyocytes via viral delivery. Methods Mol. Biol., 2014, 1181, 215-228.
[] [PMID: 25070340]
Park, S.A.; Lee, S-R.; Tung, L.; Yue, D.T. Optical mapping of optogenetically shaped cardiac action potentials. Sci. Rep., 2014, 4(1), 6125.
[] [PMID: 25135113]
Nussinovitch, U.; Shinnawi, R.; Gepstein, L. Modulation of cardiac tissue electrophysiological properties with light-sensitive proteins. Cardiovasc. Res., 2014, 102(1), 176-187.
[] [PMID: 24518144]
Zhuge, Y.; Patlolla, B.; Ramakrishnan, C.; Beygui, R.E.; Zarins, C.K.; Deisseroth, K.; Kuhl, E.; Abilez, O.J. Human pluripotent stem cell tools for cardiac optogenetics 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE, 2014.
Yu, L.; Zhou, L.; Cao, G.; Po, S.S.; Huang, B.; Zhou, X.; Wang, M.; Yuan, S.; Wang, Z.; Wang, S.; Jiang, H. optogenetic modulation of cardiac sympathetic nerve activity to prevent ventricular arrhythmias. J. Am. Coll. Cardiol., 2017, 70(22), 2778-2790.
[] [PMID: 29191327]
Watanabe, M.; Feola, I.; Majumder, R.; Jangsangthong, W.; Teplenin, A.S.; Ypey, D.L.; Schalij, M.J.; Zeppenfeld, K.; de Vries, A.A.F.; Pijnappels, D.A. Optogenetic manipulation of anatomical re-entry by light-guided generation of a reversible local conduction block. Cardiovasc. Res., 2017, 113(3), 354-366.
[] [PMID: 28395022]
Nyns, E.C.A.; Kip, A.; Bart, C.I.; Plomp, J.J.; Zeppenfeld, K.; Schalij, M.J.; de Vries, A.A.F.; Pijnappels, D.A. Optogenetic termination of ventricular arrhythmias in the whole heart: Towards biological cardiac rhythm management. Eur. Heart J., 2017, 38(27), 2132-2136.
[] [PMID: 28011703]
Nussinovitch, U.; Gepstein, L. Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nat. Biotechnol., 2015, 33(7), 750-754.
[] [PMID: 26098449]
Richter, C.; Christoph, J.; Lehnart, S.E.; Luther, S. Optogenetic Light Crafting Tools for the Control of Cardiac Arrhythmias; Methods in Molecular Biology; Springer New York, 2016, pp. 293-302.
Nussinovitch, U.; Gepstein, L. Optogenetics for suppression of cardiac electrical activity in human and rat cardiomyocyte cultures. Neurophotonics, 2015, 2(3) 031204
[] [PMID: 26158013]
Jia, Z.; Valiunas, V.; Lu, Z.; Bien, H.; Liu, H.; Wang, H-Z.; Rosati, B.; Brink, P.R.; Cohen, I.S.; Entcheva, E. Stimulating cardiac muscle by light: Cardiac optogenetics by cell delivery. Circ. Arrhythm. Electrophysiol., 2011, 4(5), 753-760.
[] [PMID: 21828312]
Prando, V.; Da Broi, F.; Franzoso, M.; Plazzo, A.P.; Pianca, N.; Francolini, M.; Basso, C.; Kay, M.W.; Zaglia, T.; Mongillo, M. Dynamics of neuroeffector coupling at cardiac sympathetic synapses. J. Physiol., 2018, 596(11), 2055-2075.
[] [PMID: 29524231]
Malloy, C.; Sifers, J.; Mikos, A.; Samadi, A.; Omar, A.; Hermanns, C.; Cooper, R.L. Using optogenetics to assess neuroendocrine modulation of heart rate in Drosophila melanogaster larvae. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol., 2017, 203(10), 791-806.
[] [PMID: 28612236]
Hulsmans, M.; Clauss, S.; Xiao, L.; Aguirre, A.D.; King, K.R.; Hanley, A.; Hucker, W.J.; Wülfers, E.M.; Seemann, G.; Courties, G.; Iwamoto, Y.; Sun, Y.; Savol, A.J.; Sager, H.B.; Lavine, K.J.; Fishbein, G.A.; Capen, D.E.; Da Silva, N.; Miquerol, L.; Wakimoto, H.; Seidman, C.E.; Seidman, J.G.; Sadreyev, R.I.; Naxerova, K.; Mitchell, R.N.; Brown, D.; Libby, P.; Weissleder, R.; Swirski, F.K.; Kohl, P.; Vinegoni, C.; Milan, D.J.; Ellinor, P.T.; Nahrendorf, M. macrophages facilitate electrical conduction in the heart. Cell, 2017, 169(3), 510-522.e20.
[] [PMID: 28431249]
Wang, Y.; Lin, W.K.; Crawford, W.; Ni, H.; Bolton, E.L.; Khan, H.; Shanks, J.; Bub, G.; Wang, X.; Paterson, D.J.; Zhang, H.; Galione, A.; Ebert, S.N.; Terrar, D.A.; Lei, M. optogenetic control of heart rhythm by selective stimulation of cardiomyocytes derived from pnmt+ cells in murine heart. Sci. Rep., 2017, 7, 40687.
[] [PMID: 28084430]
Bruegmann, T.; Boyle, P.M.; Vogt, C.C.; Karathanos, T.V.; Arevalo, H.J.; Fleischmann, B.K.; Trayanova, N.A.; Sasse, P. Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations. J. Clin. Invest., 2016, 126(10), 3894-3904.
[] [PMID: 27617859]
Zhu, Y.C.; Uradu, H.; Majeed, Z.R.; Cooper, R.L. Optogenetic stimulation of Drosophila heart rate at different temperatures and Ca2+ concentrations. Physiol. Rep., 2016, 4(3) e12695
[] [PMID: 26834237]
Zaglia, T.; Pianca, N.; Borile, G.; Da Broi, F.; Richter, C.; Campione, M.; Lehnart, S.E.; Luther, S.; Corrado, D.; Miquerol, L.; Mongillo, M. Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2. Proc. Natl. Acad. Sci. USA, 2015, 112(32), E4495-E4504.
[] [PMID: 26204914]
Ambrosi, C.M.; Sadananda, G.; Klimas, A.; Entcheva, E. Adeno-associated virus mediated gene delivery: Implications for scalable in vitro and in vivo cardiac optogenetic models. Front. Physiol., 2019, 10, 168.
Dittami, G.M.; Rajguru, S.M.; Lasher, R.A.; Hitchcock, R.W.; Rabbitt, R.D. Intracellular calcium transients evoked by pulsed infrared radiation in neonatal cardiomyocytes. J. Physiol., 2011, 589(6), 1295-306.
Savchenko, A.; Cherkas, V.; Liu, C.; Braun, G.B.; Kleschevnikov, A.; Miller, Y.I.; Molokanova, E. Graphene biointerfaces for optical stimulation of cells. Sci. Adv., 2018, 4(5) eaat0351
[] [PMID: 29795786]
Yamanaka, S. A fresh look at iPS cells. Cell, 2009, 137(1), 13-17.
[] [PMID: 19345179]
Stacey, G. Stem Cell Banking: A Global View; Methods in Molecular Biology; Springer New York, 2017, pp. 3-10.
Bellin, M.; Mummery, C.L. Inherited heart disease - what can we expect from the second decade of human iPS cell research? FEBS Lett., 2016, 590(15), 2482-2493.
[] [PMID: 27391414]
Yang, X.; Pabon, L.; Murry, C.E. Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes. Circ. Res., 2014, 114(3), 511-523.
[] [PMID: 24481842]
Yang, X.; Rodriguez, M.; Pabon, L.; Fischer, K.A.; Reinecke, H.; Regnier, M.; Sniadecki, N.J.; Ruohola-Baker, H.; Murry, C.E. Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J. Mol. Cell. Cardiol., 2014, 72, 296-304.
[] [PMID: 24735830]
Kosmidis, G.; Bellin, M.; Ribeiro, M.C.; van Meer, B.; Ward-van Oostwaard, D.; Passier, R.; Tertoolen, L.G.J.; Mummery, C.L.; Casini, S. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure. Biochem. Biophys. Res. Commun., 2015, 467(4), 998-1005.
[] [PMID: 26456652]
McCain, M.L.; Yuan, H.; Pasqualini, F.S.; Campbell, P.H.; Parker, K.K. Matrix elasticity regulates the optimal cardiac myocyte shape for contractility. Am. J. Physiol. Heart Circ. Physiol., 2014, 306(11), H1525-H1539.
[] [PMID: 24682394]
Werley, C.A.; Chien, M-P.; Gaublomme, J.; Shekhar, K.; Butty, V.; Yi, B.A.; Kralj, J.M.; Bloxham, W.; Boyer, L.A.; Regev, A.; Cohen, A.E. Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing. PLoS One, 2017, 12(3) e0172671
[] [PMID: 28333933]
Giacomelli, E.; Bellin, M.; Sala, L.; van Meer, B.J.; Tertoolen, L.G.J.; Orlova, V.V.; Mummery, C.L. Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells. Development, 2017, 144(6), 1008-1017.
[] [PMID: 28279973]
Zimmermann, W-H.; Schneiderbanger, K.; Schubert, P.; Didié, M.; Münzel, F.; Heubach, J.F.; Kostin, S.; Neuhuber, W.L.; Eschenhagen, T. Tissue engineering of a differentiated cardiac muscle construct. Circ. Res., 2002, 90(2), 223-230.
[] [PMID: 11834716]
Tiburcy, M.; Didié, M.; Boy, O.; Christalla, P.; Döker, S.; Naito, H.; Karikkineth, B.C.; El-Armouche, A.; Grimm, M.; Nose, M.; Eschenhagen, T.; Zieseniss, A.; Katschinksi, D.M.; Hamdani, N.; Linke, W.A.; Yin, X.; Mayr, M.; Zimmermann, W-H. Terminal differentiation, advanced organotypic maturation, and modeling of hypertrophic growth in engineered heart tissue. Circ. Res., 2011, 109(10), 1105-1114.
[] [PMID: 21921264]
Hirt, M.N.; Boeddinghaus, J.; Mitchell, A.; Schaaf, S.; Börnchen, C.; Müller, C.; Schulz, H.; Hubner, N.; Stenzig, J.; Stoehr, A.; Neuber, C.; Eder, A.; Luther, P.K.; Hansen, A.; Eschenhagen, T. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J. Mol. Cell. Cardiol., 2014, 74, 151-161.
[] [PMID: 24852842]
Ronaldson-Bouchard, K.; Ma, S.P.; Yeager, K.; Chen, T.; Song, L.; Sirabella, D.; Morikawa, K.; Teles, D.; Yazawa, M.; Vunjak-Novakovic, G. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature, 2018, 556(7700), 239-243.
[] [PMID: 29618819]
MacQueen, L.A.; Sheehy, S.P.; Chantre, C.O.; Zimmerman, J.F.; Pasqualini, F.S.; Liu, X.; Goss, J.A.; Campbell, P.H.; Gonzalez, G.M.; Park, S-J.; Capulli, A.K.; Ferrier, J.P.; Kosar, T.F.; Mahadevan, L.; Pu, W.T.; Parker, K.K. A tissue-engineered scale model of the heart ventricle. Nat. Biomed. Eng., 2018, 2(12), 930-941.
[] [PMID: 31015723]
Rodriguez, B.; Carusi, A.; Abi-Gerges, N.; Ariga, R.; Britton, O.; Bub, G.; Bueno-Orovio, A.; Burton, R.A.; Carapella, V.; Cardone-Noott, L.; Daniels, M.J.; Davies, M.R.; Dutta, S.; Ghetti, A.; Grau, V.; Harmer, S.; Kopljar, I.; Lambiase, P.; Lu, H.R.; Lyon, A.; Minchole, A.; Muszkiewicz, A.; Oster, J.; Paci, M.; Passini, E.; Severi, S.; Taggart, P.; Tinker, A.; Valentin, J.P.; Varro, A.; Wallman, M.; Zhou, X. Human-based approaches to pharmacology and cardiology: An interdisciplinary and intersectorial workshop. Europace, 2016, 18(9), 1287-1298.
[] [PMID: 26622055]
Brandão, K.O.; Tabel, V.A.; Atsma, D.E.; Mummery, C.L.; Davis, R.P. Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies. Dis. Model. Mech., 2017, 10(9), 1039-1059.
[] [PMID: 28883014]
Du, D.T.; Hellen, N.; Kane, C.; Terracciano, C.M. Action potential morphology of human induced pluripotent stem cell-derived cardiomyocytes does not predict cardiac chamber specificity and is dependent on cell density. Biophys. J., 2015, 108(1), 1-4.
[] [PMID: 25564842]
Sauer, A.J.; Moss, A.J.; McNitt, S.; Peterson, D.R.; Zareba, W.; Robinson, J.L.; Qi, M.; Goldenberg, I.; Hobbs, J.B.; Ackerman, M.J.; Benhorin, J.; Hall, W.J.; Kaufman, E.S.; Locati, E.H.; Napolitano, C.; Priori, S.G.; Schwartz, P.J.; Towbin, J.A.; Vincent, G.M.; Zhang, L. Long QT syndrome in adults. J. Am. Coll. Cardiol., 2007, 49(3), 329-337.
[] [PMID: 17239714]

© 2022 Bentham Science Publishers | Privacy Policy