Approach to Neurotoxicity using Human iPSC Neurons: Consortium for Safety Assessment using Human iPS Cells

Author(s): Takafumi Shirakawa, Ikuro Suzuki*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 9 , 2020


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Graphical Abstract:


Abstract:

Neurotoxicity, as well as cardiotoxicity and hepatotoxicity, resulting from administration of a test article is considered a major adverse effect both pre-clinically and clinically. Among the different types of neurotoxicity occurring during the drug development process, seizure is one of the most serious one. Seizure occurrence is usually assessed using in vivo animal models, the Functional Observational Battery, the Irwin test or electroencephalograms. In in vitro studies, a number of assessments can be performed using animal organs/cells. Interestingly, recent developments in stem cell biology, especially the development of Human-Induced Pluripotent Stem (iPS) cells, are enabling the assessment of neurotoxicity in human iPS cell-derived neurons. Further, a Multi-Electrode Array (MEA) using rodent neurons is a useful tool for identifying seizure-inducing compounds. The Consortium for Safety Assessment using Human iPS Cells (CSAHi; http://csahi.org/en/) was established in 2013 by the Japan Pharmaceutical Manufacturers Association (JPMA) to verify the application of human iPS cell-derived neuronal cells to drug safety evaluation. The Neuro Team of CSAHi has been attempting to evaluate the seizure risk of compounds using the MEA platform. Here, we review the current status of neurotoxicity and recent work, including problems related to the use of the MEA assay with human iPS neuronal cell-derived neurons, and future developments.

Keywords: Human iPS cells, cardiotoxicity, Multi-Electrode Array (MEA), neurotoxicity, EEG, seizure-inducing compounds.

[1]
Watkins, P.B. Drug safety sciences and the bottleneck in drug development. Clin. Pharmacol. Ther., 2011, 89(6), 788-790.
[http://dx.doi.org/10.1038/clpt.2011.63] [PMID: 21593756]
[2]
Nagayama, T. Adverse drug reactions for medicine newly approved in Japan from 1999 to 2013: Syncope/loss of consciousness and seizures/convulsions. Regul. Toxicol. Pharmacol., 2015, 72(3), 572-577.
[http://dx.doi.org/10.1016/j.yrtph.2015.05.030] [PMID: 26056066]
[3]
Authier, S.; Arezzo, J.; Delatte, M.S.; Kallman, M.J.; Markgraf, C.; Paquette, D.; Pugsley, M.K.; Ratcliffe, S.; Redfern, W.S.; Stevens, J.; Valentin, J.P.; Vargas, H.M.; Curtis, M.J. Safety pharmacology investigations on the nervous system: An industry survey. J. Pharmacol. Toxicol. Methods, 2016, 81, 37-46.
[http://dx.doi.org/10.1016/j.vascn.2016.06.001] [PMID: 27263834]
[4]
Irwin, S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacology (Berl.), 1968, 13(3), 222-257.
[http://dx.doi.org/10.1007/BF00401402] [PMID: 5679627]
[5]
Moser, V.C.; MacPhail, R.C. Comparative sensitivity of neurobehavioral tests for chemical screening. Neurotoxicology, 1990, 11(2), 335-344.
[PMID: 2234549]
[6]
Bassett, L.; Troncy, E.; Pouliot, M.; Paquette, D.; Ascah, A.; Authier, S. Telemetry video-Electroencephalography (EEG) in rats, dogs and non-human primates: Methods in follow-up safety pharmacology seizure liability assessments. J. Pharmacol. Toxicol. Methods, 2014, 70(3), 230-240.
[http://dx.doi.org/10.1016/j.vascn.2014.07.005] [PMID: 25065541]
[7]
Niederhauser, J.J.; Esteller, R.; Echauz, J.; Vachtsevanos, G.; Litt, B. Detection of seizure precursors from depth-EEG using a sign periodogram transform. IEEE Trans. Biomed. Eng., 2003, 50(4), 449-458.
[http://dx.doi.org/10.1109/TBME.2003.809497 PMID: 12723056]
[8]
Authier, S.; Accardi, M.V.; Paquette, D.; Pouliot, M.; Arezzo, J.; Stubbs, R.J.; Gerson, R.J.; Friedhoff, L.T.; Weis, H. Functional neurotoxicity evaluation of noribogaine using video-EEG in cynomolgus monkeys. J. Pharmacol. Toxicol. Methods, 2016, 81, 306-312.
[http://dx.doi.org/10.1016/j.vascn.2016.04.012] [PMID: 27126304]
[9]
Authier, S.; Delatte, M.S.; Kallman, M.J.; Stevens, J.; Markgraf, C. EEG in non-clinical drug safety assessments: Current and emerging considerations. J. Pharmacol. Toxicol. Methods, 2016, 81, 274-285.
[http://dx.doi.org/10.1016/j.vascn.2016.03.002] [PMID: 26992360]
[10]
Hiolski, E.M.; Ito, S.; Beggs, J.M.; Lefebvre, K.A.; Litke, A.M.; Smith, D.R. Domoic acid disrupts the activity and connectivity of neuronal networks in organotypic brain slice cultures. Neurotoxicology, 2016, 56, 215-224.
[http://dx.doi.org/10.1016/j.neuro.2016.08.004] [PMID: 27506300]
[11]
Liu, J.J.; Ding, X.Y.; Xiang, L.; Zhao, F.; Huang, S.L. A novel method for oxygen glucose deprivation model in organotypic spinal cord slices. Brain Res. Bull., 2017, 135, 163-169.
[http://dx.doi.org/10.1016/j.brainresbull.2017.10.010 PMID: 29054697]
[12]
Koerling, A.L.; Fuchsberger, T.; Paulsen, O.; Hay, Y.A. Partial restoration of physiological UP-state activity by GABA pathway modulation in an acute brain slice model of epilepsy. Neuropharmacology, 2019, 148, 394-405.
[PMID: 30472273]
[13]
Dichter, A.M.; Pollard, J. Cell culture models for studying epilepsy. Models Seizures Epilepsy, 2006, 23-34.
[14]
Bradley, J.A.; Luithardt, H.H.; Metea, M.R.; Strock, C.J. Vitro screening for seizure liability using microelectrode array technology. Toxicol. Sci., 2018, 163(1), 240-253.
[http://dx.doi.org/10.1093/toxsci/kfy029]
[15]
Kreir, M.; Van Deuren, B.; Versweyveld, S.; De Bondt, A.; Van den Wyngaert, I.; Van der Linde, H.; Lu, H.R.; Teuns, G.; Gallacher, D.J. Do in vitro assays in rat primary neurons predict drug induced seizure liability in humans? Toxicol. Appl. Pharmacol., 2018, 346, 45-57.
[http://dx.doi.org/10.1016/j.taap.2018.03.028] [PMID: 29596924]
[16]
Accardi, M.V.; Huang, H.; Authier, S. Seizure liability assessments using the hippocampal tissue slice: Comparison of non-clinical species. J. Pharmacol. Toxicol. Methods, 2018, 93, 59-68.
[http://dx.doi.org/10.1016/j.vascn.2017.11.003] [PMID: 29155282]
[17]
Cunliffe, V.T. Building a zebrafish toolkit for investigating the pathobiology of epilepsy and identifying new treatments for epileptic seizures. J. Neurosci. Methods, 2016, 260, 91-95.
[http://dx.doi.org/10.1016/j.jneumeth.2015.07.015 PMID: 26219659]
[18]
Grainger, A.I.; King, M.C.; Nagel, D.A.; Parri, H.R.; Coleman, M.D.; Hill, E.J. In vitro models for seizure-liability testing using induced pluripotent stem cells. Front. Neurosci., 2018, 12, 590.
[http://dx.doi.org/10.3389/fnins.2018.00590] [PMID: 30233290]
[19]
Thomson, J.A.; Itskovitz-Eldor, J.; Shapiro, S.S.; Waknitz, M.A.; Swiergiel, J.J.; Marshall, V.S.; Jones, J.M. Embryonic stem cell lines derived from human blastocysts. Science, 1998, 282(5391), 1145-1147.
[http://dx.doi.org/10.1126/science.282.5391.1145 PMID: 9804556]
[20]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4), 663-676.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[21]
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, 2007, 131(5), 861-872.
[http://dx.doi.org/10.1016/j.cell.2007.11.019] [PMID: 18035408]
[22]
McCaughey-Chapman, A.; Connor, B. Human cortical neuron generation using cell reprogramming: A review of recent advances. Stem Cells Dev., 2018, 27(24), 1674-1692.
[http://dx.doi.org/10.1089/scd.2018.0122] [PMID: 30343634]
[23]
Shi, Y.; Kirwan, P.; Smith, J.; Robinson, H.P.; Livesey, F.J. Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat. Neurosci., 2012, 15(3), 477-861.
[http://dx.doi.org/10.1038/nn.3041] [PMID: 30343634]
[24]
Shaltouki, A.; Peng, J.; Liu, Q.; Rao, M.S.; Zeng, X. Efficient generation of astrocytes from human pluripotent stem cells in defined conditions. Stem Cells, 2013, 31(5), 941-952.
[http://dx.doi.org/10.1002/stem.1334] [PMID: 23341249]
[25]
Liu, Y.; Liu, H.; Sauvey, C.; Yao, L.; Zarnowska, E.D.; Zhang, S.C. Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat. Protoc., 2013, 8(9), 1670-1679.
[http://dx.doi.org/10.1038/nprot.2013.106] [PMID: 23928500]
[26]
Kim, T.G.; Yao, R.; Monnell, T.; Cho, J.H.; Vasudevan, A.; Koh, A.; Peeyush, K.T.; Moon, M.; Datta, D.; Bolshakov, V.Y.; Kim, K.S.; Chung, S. Efficient specification of interneurons from human pluripotent stem cells by dorsoventral and rostrocaudal modulation. Stem Cells, 2014, 32(7), 1789-1804.
[http://dx.doi.org/10.1002/stem.1704] [PMID: 24648391]
[27]
Herculano-Houzel, S. The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia, 2014, 62(9), 1377-1391.
[http://dx.doi.org/10.1002/glia.22683] [PMID: 24807023]
[28]
Zhang, W.; Peterson, M.; Beyer, B.; Frankel, W.N.; Zhang, Z.W. Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J. Neurosci., 2014, 34(7), 2754-2763.
[http://dx.doi.org/10.1523/JNEUROSCI.4900-12.2014 PMID: 24523563]
[29]
Sun, Y.; Paşca, S.P.; Portmann, T.; Goold, C.; Worringer, K.A.; Guan, W.; Chan, K.C.; Gai, H.; Vogt, D.; Chen, Y.J.; Mao, R.; Chan, K.; Rubenstein, J.L.; Madison, D.V.; Hallmayer, J.; Froehlich-Santino, W.M.; Bernstein, J.A.; Dolmetsch, R.E. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. eLife, 2016, 5, 5.
[http://dx.doi.org/10.7554/eLife.13073] [PMID: 27458797]
[30]
Ortolano, S.; Vieitez, I.; Agis-Balboa, R.C.; Spuch, C. Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease. Mol. Brain, 2014, 7, 7.
[http://dx.doi.org/10.1186/1756-6606-7-7] [PMID: 24472629]
[31]
Rossignol, E.; Kruglikov, I.; van den Maagdenberg, A.M.; Rudy, B.; Fishell, G. CaV 2.1 ablation in cortical interneurons selectively impairs fast-spiking basket cells and causes generalized seizures. Ann. Neurol., 2013, 74(2), 209-222.
[PMID: 23595603]
[32]
Jiang, X.; Lachance, M.; Rossignol, E. Involvement of cortical fastspiking parvalbumin-positive basket cells in epilepsy. Prog. Brain Res., 2016, 226, 81-126.
[http://dx.doi.org/10.1016/bs.pbr.2016.04.012] [PMID: 27323940]
[33]
Hedreen, J.C.; Peyser, C.E.; Folstein, S.E.; Ross, C.A. Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci. Lett., 1991, 133(2), 257-261.
[http://dx.doi.org/10.1016/0304-3940(91)90583-F PMID: 1840078]
[34]
Heilker, R.; Traub, S.; Reinhardt, P.; Schöler, H.R.; Sterneckert, J. iPS cell derived neuronal cells for drug discovery. Trends Pharmacol. Sci., 2014, 35(10), 510-519.
[http://dx.doi.org/10.1016/j.tips.2014.07.003] [PMID: 25096281]
[35]
Wheeler, H.E.; Wing, C.; Delaney, S.M.; Komatsu, M.; Dolan, M.E. Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells. PLoS One, 2015, 10(2) e0118020
[http://dx.doi.org/10.1371/journal.pone.0118020 PMID: 25689802]
[36]
Pei, Y.; Peng, J.; Behl, M.; Sipes, N. S.; Shockley, K. R.; Rao, M. S.; Tice, R. R.; Zeng, X. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. Brain Res., 2016, 1638(Pt A), 57-73.
[37]
Ohara, R.; Imamura, K.; Morii, F.; Egawa, N.; Tsukita, K.; Enami, T.; Shibukawa, R.; Mizuno, T.; Nakagawa, M.; Inoue, H. Modeling drug-induced neuropathy using human iPSCs for predictive toxicology. Clin. Pharmacol. Ther., 2017, 101(6), 754-762.
[http://dx.doi.org/10.1002/cpt.562] [PMID: 27859025]
[38]
Thomas, C.A., Jr; Springer, P.A.; Loeb, G.E.; Berwald-Netter, Y.; Okun, L.M. A miniature microelectrode array to monitor the bioelectric activity of cultured cells. Exp. Cell Res., 1972, 74(1), 61-66.
[http://dx.doi.org/10.1016/0014-4827(72)90481-8 PMID: 4672477]
[39]
Gross, G.W. Simultaneous single unit recording in vitro with a photoetched laser deinsulated gold multimicroelectrode surface. IEEE Trans. Biomed. Eng., 1979, 26(5), 273-279.
[http://dx.doi.org/10.1109/TBME.1979.326402] [PMID: 447356]
[40]
Pine, J. Recording action potentials from cultured neurons with extracellular microcircuit electrodes. J. Neurosci. Methods, 1980, 2(1), 19-31.
[http://dx.doi.org/10.1016/0165-0270(80)90042-4 PMID: 7329089]
[41]
Wheeler, B.C.; Novak, J.L. Current source density estimation using microelectrode array data from the hippocampal slice preparation. IEEE Trans. Biomed. Eng., 1986, 33(12), 1204-1212.
[http://dx.doi.org/10.1109/TBME.1986.325701] [PMID: 3817854]
[42]
Jimbo, Y.; Tateno, T.; Robinson, H.P. Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons. Biophys. J., 1999, 76(2), 670-678.
[http://dx.doi.org/10.1016/S0006-3495(99)77234-6 PMID: 9929472]
[43]
Wagenaar, D.A.; Madhavan, R.; Pine, J.; Potter, S.M. Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation. J. Neurosci., 2005, 25(3), 680-688.
[http://dx.doi.org/10.1523/JNEUROSCI.4209-04.2005] [PMID: 15659605]
[44]
Zeck, G.; Fromherz, P. Noninvasive neuroelectronic interfacing with synaptically connected snail neurons immobilized on a semiconductor chip. Proc. Natl. Acad. Sci. USA, 2001, 98(18), 10457-10462.
[http://dx.doi.org/10.1073/pnas.181348698] [PMID: 11526244]
[45]
Bakkum, D.J.; Frey, U.; Radivojevic, M.; Russell, T.L.; Müller, J.; Fiscella, M.; Takahashi, H.; Hierlemann, A. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites. Nat. Commun., 2013, 4, 2181.
[http://dx.doi.org/10.1038/ncomms3181] [PMID: 23867868]
[46]
Obien, M.E.; Deligkaris, K.; Bullmann, T.; Bakkum, D.J.; Frey, U. Revealing neuronal function through microelectrode array recordings. Front. Neurosci., 2015, 8, 423.
[http://dx.doi.org/10.3389/fnins.2014.00423] [PMID: 25610364]
[47]
Ronchi, S.; Fiscella, M.; Marchetti, C.; Viswam, V.; Müller, J.; Frey, U.; Hierlemann, A. Single-cell electrical stimulation using CMOS-based high-density microelectrode arrays. Front. Neurosci., 2019, 13, 208.
[http://dx.doi.org/10.3389/fnins.2019.00208] [PMID: 30918481]
[48]
Johnstone, A.F.; Gross, G.W.; Weiss, D.G.; Schroeder, O.H.; Gramowski, A.; Shafer, T.J. Microelectrode arrays: A physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology, 2010, 31(4), 331-350.
[http://dx.doi.org/10.1016/j.neuro.2010.04.001] [PMID: 20399226]
[49]
Frega, M.; Pasquale, V.; Tedesco, M.; Marcoli, M.; Contestabile, A.; Nanni, M.; Bonzano, L.; Maura, G.; Chiappalone, M. Cortical cultures coupled to micro-electrode arrays: A novel approach to perform in vitro excitotoxicity testing. Neurotoxicol. Teratol., 2012, 34(1), 116-127.
[http://dx.doi.org/10.1016/j.ntt.2011.08.001] [PMID: 21856414]
[50]
Mack, C.M.; Lin, B.J.; Turner, J.D.; Johnstone, A.F.; Burgoon, L.D.; Shafer, T.J. Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes. Neurotoxicology, 2014, 40, 75-85.
[http://dx.doi.org/10.1016/j.neuro.2013.11.008] [PMID: 24325902]
[51]
Nicolas, J.; Hendriksen, P.J.; van Kleef, R.G.; de Groot, A.; Bovee, T.F.; Rietjens, I.M.; Westerink, R.H. Detection of marine neurotoxins in food safety testing using a multielectrode array. Mol. Nutr. Food Res., 2014, 58(12), 2369-2378.
[http://dx.doi.org/10.1002/mnfr.201400479] [PMID: 25266399]
[52]
Pancrazio, J.J.; Gopal, K.; Keefer, E.W.; Gross, G.W. Botulinum toxin suppression of CNS network activity in vitro. J. Toxicol., 2014, 2014, 732913
[http://dx.doi.org/10.1155/2014/732913] [PMID: 24688538]
[53]
Alloisio, S.; Giussani, V.; Nobile, M.; Chiantore, M.; Novellino, A. Microelectrode Array (MEA) platform as a sensitive tool to detect and evaluate Ostreopsis cf. ovata toxicity. Harmful Algae, 2016, 55, 230-237.
[http://dx.doi.org/10.1016/j.hal.2016.03.001] [PMID: 28073536]
[54]
Hondebrink, L.; Verboven, A.H.A.; Drega, W.S.; Schmeink, S.; de Groot, M.W.G.D.M.; van Kleef, R.G.D.M.; Wijnolts, F.M.J.; de Groot, A.; Meulenbelt, J.; Westerink, R.H.S. Neurotoxicity screening of (illicit) drugs using novel methods for analysis of Microelectrode Array (MEA) recordings. Neurotoxicology, 2016, 55, 1-9.
[http://dx.doi.org/10.1016/j.neuro.2016.04.020] [PMID: 27149913]
[55]
Bradley, J.A.; Strock, C.J. Screening for neurotoxicity with microelectrode array. Curr. Protoc. Toxicol., 2019, 79(1) e67
[http://dx.doi.org/10.1002/cptx.67] [PMID: 30575314]
[56]
Fan, J.; Thalody, G.; Kwagh, J.; Burnett, E.; Shi, H.; Lewen, G.; Chen, S.J.; Levesque, P. Assessing seizure liability using multi-electrode arrays (MEA). Toxicol. In Vitro, 2019, 55, 93-100.
[57]
Kasteel, E.E.; Westerink, R.H. Comparison of the acute inhibitory effects of Tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes. Toxicol. Lett., 2017, 270, 12-16.
[http://dx.doi.org/10.1016/j.toxlet.2017.02.014] [PMID: 28192153]
[58]
Odawara, A.; Saitoh, Y.; Alhebshi, A.H.; Gotoh, M.; Suzuki, I. Long-term electrophysiological activity and pharmacological response of a human induced pluripotent stem cell-derived neuron and astrocyte co-culture. Biochem. Biophys. Res. Commun., 2014, 443(4), 1176-1181.
[http://dx.doi.org/10.1016/j.bbrc.2013.12.142] [PMID: 24406164]
[59]
Amin, H.; Maccione, A.; Marinaro, F.; Zordan, S.; Nieus, T.; Berdondini, L. Electrical responses and spontaneous activity of human iPS-derived neuronal networks characterized for 3-month culture with 4096-electrode arrays. Front. Neurosci., 2016, 10, 121.
[http://dx.doi.org/10.3389/fnins.2016.00121] [PMID: 27065786]
[60]
Odawara, A.; Katoh, H.; Matsuda, N.; Suzuki, I. Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons. Biochem. Biophys. Res. Commun., 2016, 469(4), 856-862.
[http://dx.doi.org/10.1016/j.bbrc.2015.12.087] [PMID: 26718408]
[61]
Odawara, A.; Katoh, H.; Matsuda, N.; Suzuki, I. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. Sci. Rep., 2016, 6, 26181.
[http://dx.doi.org/10.1038/srep26181] [PMID: 27188845]
[62]
Frega, M.; van Gestel, S.H.; Linda, K.; van der Raadt, J.; Keller, J.; Van Rhijn, J.R.; Schubert, D.; Albers, C.A.; Nadif Kasri, N. Rapid neuronal differentiation of induced pluripotent stem cells for measuring network activity on micro-electrode arrays. J. Vis. Exp., 2017, (119), 54900.
[http://dx.doi.org/10.1016/j.tox.2017.06.010] [PMID: 28666936]
[63]
Ishii, M.N.; Yamamoto, K.; Shoji, M.; Asami, A.; Kawamata, Y. Human Induced Pluripotent Stem Cell (hiPSC)-derived neurons respond to convulsant drugs when co-cultured with hiPSC-derived astrocytes. Toxicology, 2017, 389, 130-138.
[http://dx.doi.org/10.1016/j.tox.2017.06.010] [PMID: 28666936]
[64]
Seidel, D.; Jahnke, H.G.; Englich, B.; Girard, M.; Robitzki, A.A. In vitro field potential monitoring on a multi-microelectrode array for the electrophysiological long-term screening of neural stem cell maturation. Analyst (Lond.), 2017, 142(11), 1929-1937.
[http://dx.doi.org/10.1039/C6AN02713J] [PMID: 28484750]
[65]
Matsuda, N.; Odawara, A.; Katoh, H.; Okuyama, N.; Yokoi, R.; Suzuki, I. Detection of synchronized burst firing in cultured human induced pluripotent stem cell-derived neurons using a 4-step method. Biochem. Biophys. Res. Commun., 2018, 497(2), 612-618.
[http://dx.doi.org/10.1016/j.bbrc.2018.02.117] [PMID: 29454965]
[66]
Odawara, A.; Matsuda, N.; Ishibashi, Y.; Yokoi, R.; Suzuki, I. Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system. Sci. Rep., 2018, 8(1), 10416.
[http://dx.doi.org/10.1038/s41598-018-28835-7 PMID: 29991696]
[67]
Ojima, A.; Miyamoto, N. Method for MEA data analysis of drug-treated rat primary neurons and human iPSC-derived neurons to evaluate the risk of drug-induced seizures. Yakugaku Zasshi, 2018, 138(6), 823-828.
[http://dx.doi.org/10.1248/yakushi.17-00213-3] [PMID: 29863054]
[68]
Tukker, A.M.; Wijnolts, F.M.J.; de Groot, A.; Westerink, R.H.S. Human iPSC-derived neuronal models for in vitro neurotoxicity assessment. Neurotoxicology, 2018, 67, 215-225.
[http://dx.doi.org/10.1016/j.neuro.2018.06.007] [PMID: 29909083]
[69]
Yokoi, R.; Okabe, M.; Matsuda, N.; Odawara, A.; Karashima, A.; Suzuki, I. Impact of sleep-wake-associated neuromodulators and repetitive low-frequency stimulation on human iPSC-derived neurons. Front. Neurosci., 2019, 13, 554.
[http://dx.doi.org/10.3389/fnins.2019.00554] [PMID: 31191238]
[70]
Matsuda, N.; Odawara, A.; Okamura, A.; Kinoshita, K.; Shirakawa, T.; Suzukki, I. Analysis of convulsant-induced firings in cultured human iPS cell-derived neurons using deep learning. In: Neuroscience; San Diego, USA, 2018.
[71]
Ishibashi, Y.; Odawara, A.; Matsuda, N.; Suzuki, I. Vitro drug efficacy evaluation in cultured human iPSC-derived neurons using MEA system; Society of Toxicology: Baltimore, USA, 2019.
[72]
Bardy, C.; van den Hurk, M.; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Böhnke, L.; Boyer, L.; Simon, S.; Gage, F.H. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro. Proc. Natl. Acad. Sci. USA, 2015, 112(20), E2725-E2734.
[http://dx.doi.org/10.1073/pnas.1504393112] [PMID: 25870293]
[73]
Ryynänen, T.; Toivanen, M.; Salminen, T.; Ylä-Outinen, L.; Narkilahti, S.; Lekkala, J. Ion beam assisted e-beam deposited tin microelectrodes-applied to neuronal cell culture medium evaluation. Front. Neurosci., 2018, 12, 882.
[http://dx.doi.org/10.3389/fnins.2018.00882] [PMID: 30568570]
[74]
Lancaster, M.A.; Renner, M.; Martin, C.A.; Wenzel, D.; Bicknell, L.S.; Hurles, M.E.; Homfray, T.; Penninger, J.M.; Jackson, A.P.; Knoblich, J.A. Cerebral organoids model human brain development and microcephaly. Nature, 2013, 501(7467), 373-379.
[http://dx.doi.org/10.1038/nature12517] [PMID: 23995685]
[75]
Lancaster, M.A.; Knoblich, J.A. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc., 2014, 9(10), 2329-2340.
[http://dx.doi.org/10.1038/nprot.2014.158] [PMID: 25188634]
[76]
Qian, X.; Song, H.; Ming, G.L. Brain organoids: Advances, applications and challenges. Development, 2019, 146(8) 166074
[http://dx.doi.org/10.1242/dev.166074] [PMID: 30992274]
[77]
Trujillo, C.A.; Gao, R.; Negraes, P.D.; Gu, J.; Buchanan, J.; Preissl, S.; Wang, A.; Wu, W.; Haddad, G.G.; Chaim, I.A.; Domissy, A.; Vandenberghe, M.; Devor, A.; Yeo, G.W.; Voytek, B.; Muotri, A.R. Complex oscillatory waves emerging from cortical organoids model early human brain network development. complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell, 2019, 25(4), 558-569.e7.
[http://dx.doi.org/10.1016/j.stem.2019.08.002] [PMID: 31474560]


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VOLUME: 21
ISSUE: 9
Year: 2020
Page: [780 - 786]
Pages: 7
DOI: 10.2174/1389201020666191129103730
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