Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity

References

• Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663–676. PubMed PMID: 16904174.
   Google Scholar
• Clark M, Steger-Hartmann T. A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans. Regul Toxicol Pharmacol. 2018 Jul;96:94–105. PubMed PMID: 29730448.
   Google Scholar
• Herculano-Houzel S. Not all brains are made the same: new views on brain scaling in evolution. Brain Behav Evol. 2011;78(1):22–36. PubMed PMID: 21691045.
   Google Scholar
• Hofer T, Gerner I, Gundert-Remy U, et al. Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation. Arch Toxicol. 2004 Oct;78(10):549–564. PubMed PMID: 15170526.
   Google Scholar
• Alwin Prem Anand A, Gowri Sankar S, Kokila Vani V. Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons. J Cell Mol Med. 2012 Nov;16(11):2592–2610. PubMed PMID: 22863662; PubMed Central PMCID: PMC4118228.
   Google Scholar
• Xicoy H, Wieringa B, Martens GJ. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener. 2017 Jan 24;12(1):10. PubMed PMID: 28118852; PubMed Central PMCID: PMC5259880.
   Google Scholar
• Romito A, Cobellis G. Pluripotent stem cells: current understanding and future directions. Stem Cells Int. 2016;2016:9451492. PubMed PMID: 26798367; PubMed Central PMCID: PMC4699068.
   Google Scholar
• Luo Y, Rao M, Zou J. Generation of GFP reporter human induced pluripotent stem cells using AAVS1 safe harbor transcription activator-like effector nuclease. Curr Protoc Stem Cell Biol. 2014 May 16;29:1–18. 5A 7. PubMed PMID: 24838915; PubMed Central PMCID: PMC4128243.
   Google Scholar
• Den Hartogh SC, Passier R. Concise review: fluorescent reporters in human pluripotent stem cells: contributions to cardiac differentiation and their applications in cardiac disease and toxicity. Stem Cells. 2016 Jan;34(1):13–26. PubMed PMID: 26446349.
   Google Scholar
• Gonzalez F. CRISPR/Cas9 genome editing in human pluripotent stem cells: harnessing human genetics in a dish. Dev Dyn. 2016 Jul;245(7):788–806. PubMed PMID: 27145095.
   Google Scholar
• Kwart D, Paquet D, Teo S, et al. Precise and efficient scarless genome editing in stem cells using CORRECT. Nat Protoc. 2017 Feb;12(2):329–354. PubMed PMID: 28102837.
   Google Scholar
• Liang X, Potter J, Kumar S, et al. Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA. J Biotechnol. 2017 Jan;10(241):136–146. PubMed PMID: 27845164.
   Google Scholar
• Lin S, Staahl BT, Alla RK, et al. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. eLife. 2014 Dec;15(3):e04766. PubMed PMID: 25497837; PubMed Central PMCID: PMC4383097.
   Google Scholar
• Cui J, Rothstein M, Bennett T, et al. Quantification of dopaminergic neuron differentiation and neurotoxicity via a genetic reporter. Sci Rep. 2016 Apr;28(6):25181. PubMed PMID: 27121904; PubMed Central PMCID: PMC4848568.
   Google Scholar
• Xia N, Fang F, Zhang P, et al. A knockin reporter allows purification and characterization of mDA neurons from heterogeneous populations. Cell Rep. 2017 Mar 7;18(10):2533–2546. PubMed PMID: 28273465.
   Google Scholar
• Elliott DA, Braam SR, Koutsis K, et al. NKX2-5(eGFP/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat Methods. 2011 Oct 23;8(12):1037–1040. PubMed PMID: 22020065.
   Google Scholar
• Pei Y, Peng J, Behl M, et al. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. Brain Res. 2016 May 1;1638(Pt A):57–73. PubMed PMID: 26254731; PubMed Central PMCID: PMC5032144.
   Google Scholar
• Holmqvist S, Brouwer M, Djelloul M, et al. Generation of human pluripotent stem cell reporter lines for the isolation of and reporting on astrocytes generated from ventral midbrain and ventral spinal cord neural progenitors. Stem Cell Res. 2015 Jul;15(1):203–220. PubMed PMID: 26100233.
   Google Scholar
• Wu J, Hunt SD, Xue H, et al. Generation and characterization of a MYF5 reporter human iPS cell line using CRISPR/Cas9 mediated homologous recombination. Sci Rep. 2016 Jan;5(6):18759. PubMed PMID: 26729410; PubMed Central PMCID: PMC4700424.
   Google Scholar
• Wu J, Hunt SD, Xue H, et al. Generation and validation of PAX7 reporter lines from human iPS cells using CRISPR/Cas9 technology. Stem Cell Res. 2016 Mar;16(2):220–228. PubMed PMID: 26826926.
   Google Scholar
• Pei Y, Sierra G, Sivapatham R, et al. A platform for rapid generation of single and multiplexed reporters in human iPSC lines. Sci Rep. 2015 Mar;17(5):9205. PubMed PMID: 25777362; PubMed Central PMCID: PMC4361878.
   Google Scholar
• Tomizawa M, Shinozaki F, Motoyoshi Y, et al. Differentiation of human induced pluripotent stem cells in William’s E initiation medium supplemented with 3bromopyruvate and 2deoxydglucose. Mol Med Rep. 2017 Jun;15(6):3719–3723. PubMed PMID: 28440498.
   Google Scholar
• Tomizawa M, Shinozaki F, Motoyoshi Y, et al. Oncostatin M in William’s E medium is suitable for initiation of hepatocyte differentiation in human induced pluripotent stem cells. Mol Med Rep. 2017 May;15(5):3088–3092. PubMed PMID: 28358419.
   Google Scholar
• McCombs JE, Palmer AE. Measuring calcium dynamics in living cells with genetically encodable calcium indicators. Methods. 2008 Nov;46(3):152–159. PubMed PMID: 18848629; PubMed Central PMCID: PMC2654717.
   Google Scholar
• Apati A, Berecz T, Sarkadi B. Calcium signaling in human pluripotent stem cells. Cell Calcium. 2016 Mar;59(2–3):117–123. PubMed PMID: 26922096.
   Google Scholar
• Apati A, Paszty K, Erdei Z, et al. Calcium signaling in pluripotent stem cells. Mol Cell Endocrinol. 2012 Apr 28;353(1–2):57–67. PubMed PMID: 21945604.
   Google Scholar
• Vofely G, Berecz T, Szabo E, et al. Characterization of calcium signals in human induced pluripotent stem cell-derived dentate gyrus neuronal progenitors and mature neurons, stably expressing an advanced calcium indicator protein. Mol Cell Neurosci. 2018 Apr;88:222–230. PubMed PMID: 29425968.
   Google Scholar
• Shinnawi R, Huber I, Maizels L, et al. Monitoring human-induced pluripotent stem cell-derived cardiomyocytes with genetically encoded calcium and voltage fluorescent reporters. Stem Cell Reports. 2015 Oct 13;5(4):582–596. PubMed PMID: 26372632; PubMed Central PMCID: PMC4624957.
   Google Scholar
• Fraietta I, Gasparri F. The development of high-content screening (HCS) technology and its importance to drug discovery. Expert Opin Drug Discov. 2016;11(5):501–514. PubMed PMID: 26971542.
   Google Scholar
• Nerada Z, Hegyi Z, Szepesi A, et al. Application of fluorescent dye substrates for functional characterization of ABC multidrug transporters at a single cell level. Cytometry A. 2016 Sep;89(9):826–834. PubMed PMID: 27602881.
   Google Scholar
• Horvath P, Aulner N, Bickle M, et al. Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov. 2016 Nov;15(11):751–769. PubMed PMID: 27616293.
   Google Scholar
• Sirenko O, Hesley J, Rusyn I, et al. High-content assays for hepatotoxicity using induced pluripotent stem cell-derived cells. Assay Drug Dev Technol. 2014 Jan-Feb;12(1):43–54. PubMed PMID: 24229356; PubMed Central PMCID: PMC3934660.
   Google Scholar
• Trask OJ Jr., Moore A, LeCluyse EL. A micropatterned hepatocyte coculture model for assessment of liver toxicity using high-content imaging analysis. Assay Drug Dev Technol. 2014 Jan-Feb;12(1):16–27. PubMed PMID: 24444127.
   Google Scholar
• Sirenko O, Cromwell EF. Determination of hepatotoxicity in iPSC-derived hepatocytes by multiplexed high content assays. Methods Mol Biol. 2018;1683:339–354. PubMed PMID: 29082501.
   Google Scholar
• Pointon A, Abi-Gerges N, Cross MJ, et al. Phenotypic profiling of structural cardiotoxins in vitro reveals dependency on multiple mechanisms of toxicity. Toxicol Sci. 2013 Apr;132(2):317–326. PubMed PMID: 23315586.
   Google Scholar
• Pointon A, Pilling J, Dorval T, et al. From the cover: high-throughput imaging of cardiac microtissues for the assessment of cardiac contraction during drug discovery. Toxicol Sci. 2017 Feb;155(2):444–457. PubMed PMID: 28069985.
   Google Scholar
• McKeithan WL, Savchenko A, Yu MS, et al. An automated platform for assessment of congenital and drug-induced arrhythmia with hiPSC-derived cardiomyocytes. Front Physiol. 2017;8:766. PubMed PMID: 29075196; PubMed Central PMCID: PMC5641590.
   Google Scholar
• Sirenko O, Grimm FA, Ryan KR, et al. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model. Toxicol Appl Pharmacol. 2017 May;1(322):60–74. PubMed PMID: 28259702; PubMed Central PMCID: PMC5734940.
   Google Scholar
• Grimm FA, Iwata Y, Sirenko O, et al. High-content assay multiplexing for toxicity screening in induced pluripotent stem cell-derived cardiomyocytes and hepatocytes. Assay Drug Dev Technol. 2015 Nov;13(9):529–546. PubMed PMID: 26539751; PubMed Central PMCID: PMC4652224.
   Google Scholar
• Ryan KR, Sirenko O, Parham F, et al. Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity. Neuro-toxicology. 2016 Mar;53:271–281. PubMed PMID: 26854185.
   Google Scholar
• Sherman SP, Bang AG. High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons. Dis Model Mech. 2018 Feb 2;11(2). PubMed PMID: 29361516; PubMed Central PMCID: PMC5894944. DOI:10.1242/dmm.031906
   Google Scholar
• Kandasamy K, Chuah JK, Su R, et al. Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods. Sci Rep. 2015 Jul;27(5):12337. PubMed PMID: 26212763; PubMed Central PMCID: PMC4515747.
   Google Scholar
• Iwata Y, Klaren WD, Lebakken CS, et al. High-content assay multiplexing for vascular toxicity screening in induced pluripotent stem cell-derived endothelial cells and human umbilical vein endothelial cells. Assay Drug Dev Technol. 2017 Aug/Sep;15(6):267–279. PubMed PMID: 28771372; PubMed Central PMCID: PMC5576216.
   Google Scholar
• Klaren WD, Rusyn I. High-content assay multiplexing for muscle toxicity screening in human-induced pluripotent stem cell-derived skeletal myoblasts. Assay Drug Dev Technol. 2018 Aug/Sep;16(6):333–342. PubMed PMID: 30070899.
   Google Scholar
• Braam SR, Tertoolen L, van de Stolpe A, et al. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res. 2010 Mar;4(2):107–116. PubMed PMID: 20034863.
   Google Scholar
• Goineau S, Castagne V. Proarrhythmic risk assessment using conventional and new in vitro assays. Regul Toxicol Pharmacol. 2017 Aug;88:1–11. PubMed PMID: 28506844.
   Google Scholar
• Harris K, Aylott M, Cui Y, et al. Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays. Toxicol Sci. 2013 Aug;134(2):412–426. PubMed PMID: 23690542.
   Google Scholar
• Ando H, Yoshinaga T, Yamamoto W, et al. A new paradigm for drug-induced torsadogenic risk assessment using human iPS cell-derived cardiomyocytes. J Pharmacol Toxicol Methods. 2017 Mar - Apr;84:111–127. PubMed PMID: 27956204.
   Google Scholar
• 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 Aug 1;140(2):445–461. PubMed PMID: 24812011.
   Google Scholar
• Gilchrist KH, Lewis GF, Gay EA, et al. High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays. Toxicol Appl Pharmacol. 2015 Oct 15;288(2):249–257. PubMed PMID: 26232523.
   Google Scholar
• Qu Y, Vargas HM. Proarrhythmia risk assessment in human induced pluripotent stem cell-derived cardiomyocytes using the maestro MEA platform. Toxicol Sci. 2015 Sep;147(1):286–295. PubMed PMID: 26117837.
   Google Scholar
• Kasteel EE, Westerink RH. Comparison of the acute inhibitory effects of Tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes. Toxicol Lett. 2017 Mar 15;270:12–16. PubMed PMID: 28192153.
   Google Scholar
• Odawara A, Matsuda N, Ishibashi Y, et al. Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system. Sci Rep. 2018 Jul 10;8(1):10416. PubMed PMID: 29991696; PubMed Central PMCID: PMC6039442.
   Google Scholar
• Tukker AM, de Groot MW, Wijnolts FM, et al. Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons? Altex. 2016;33(3):261–271. PubMed PMID: 27010910.
   Google Scholar
• Tukker AM, Wijnolts FMJ, de Groot A, et al. Human iPSC-derived neuronal models for in vitro neurotoxicity assessment. Neurotoxicology. 2018 Jul;67:215–225. PubMed PMID: 29909083.
   Google Scholar
• Pellizzer C, Bremer S, Hartung T. Developmental toxicity testing from animal towards embryonic stem cells. Altex. 2005;22(2):47–57. PubMed PMID: 15953962.
   Google Scholar
• Tandon S, Jyoti S. Embryonic stem cells: an alternative approach to developmental toxicity testing. J Pharm Bioallied Sci. 2012 Apr;4(2):96–100. PubMed PMID: 22557918; PubMed Central PMCID: PMC3341726.
   Google Scholar
• Genschow E, Spielmann H, Scholz G, et al. The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. European centre for the validation of alternative methods. Altern Lab Anim. 2002 Mar-Apr;30(2):151–176. PubMed PMID: 11971753.
   Google Scholar
• Luz AL, Tokar EJ. Pluripotent stem cells in developmental toxicity testing: a review of methodological advances. Toxicol Sci. 2018 Sep 1;165(1):31–39. PubMed PMID: 30169765; PubMed Central PMCID: PMC6111785.
   Google Scholar
• Ginis I, Luo Y, Miura T, et al. Differences between human and mouse embryonic stem cells. Dev Biol. 2004 May 15;269(2):360–380. PubMed PMID: 15110706.
   Google Scholar
• Adler S, Pellizzer C, Hareng L, et al. First steps in establishing a developmental toxicity test method based on human embryonic stem cells. Toxicol In Vitro. 2008 Feb;22(1):200–211. PubMed PMID: 17961973.
   Google Scholar
• Worley KE, Rico-Varela J, Ho D, et al. Teratogen screening with human pluripotent stem cells. Integr Biol (Camb). 2018 Sep 17;10(9):491–501. PubMed PMID: 30095839; PubMed Central PMCID: PMC6141326.
   Google Scholar
• Czysz K, Minger S, Thomas N. DMSO efficiently down regulates pluripotency genes in human embryonic stem cells during definitive endoderm derivation and increases the proficiency of hepatic differentiation. PloS one. 2015;10(2):e0117689. PubMed PMID: 25659159; PubMed Central PMCID: PMC4320104.
   Google Scholar
• Khalid O, Kim JJ, Kim HS, et al. Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells. Stem Cell Res. 2014 May;12(3):791–806. PubMed PMID: 24751885; PubMed Central PMCID: PMC4041389.
   Google Scholar
• Jung EM, Choi YU, Kang HS, et al. Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205–218. PubMed PMID: 24737281.
   Google Scholar
• Jagtap S, Meganathan K, Gaspar J, et al. Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743–1756. PubMed PMID: 21198554; PubMed Central PMCID: PMC3081118.
   Google Scholar
• Mayshar Y, Yanuka O, Benvenisty N. Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells. J Cell Mol Med. 2011 Jun;15(6):1393–1401. PubMed PMID: 20561110; PubMed Central PMCID: PMC4373338.
   Google Scholar
• Kim H, Kim YY, Ku SY, et al. The effect of estrogen compounds on human embryoid bodies. Reprod Sci. 2013 Jun;20(6):661–669. PubMed PMID: 23184660; PubMed Central PMCID: PMC3713546.
   Google Scholar
• Jiang Y, Wang D, Zhang G, et al. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene. Environ Toxicol. 2016 Nov;31(11):1372–1380. PubMed PMID: 25847060.
   Google Scholar
• Kameoka S, Babiarz J, Kolaja K, et al. A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76–90. PubMed PMID: 24154490.
   Google Scholar
• Schulpen SH, de Jong E, de la Fonteyne LJ, et al. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol. Toxicol In Vitro. 2015 Apr;29(3):449–457. PubMed PMID: 25524013.
   Google Scholar
• Stummann TC, Hareng L, Bremer S. Hazard assessment of methylmercury toxicity to neuronal induction in embryogenesis using human embryonic stem cells. Toxicology. 2009 Mar 29;257(3):117–126. PubMed PMID: 19150642.
   Google Scholar
• He X, Imanishi S, Sone H, et al. Effects of methylmercury exposure on neuronal differentiation of mouse and human embryonic stem cells. Toxicol Lett. 2012 Jul 7;212(1):1–10. PubMed PMID: 22555245.
   Google Scholar
• Wei M, Li S, Le W. Nanomaterials modulate stem cell differen-tiation: biological interaction and underlying mechanisms. J Nanobiotechnology. 2017 Oct 25;15(1):75. PubMed PMID: 29065876; PubMed Central PMCID: PMC5655945.
   Google Scholar
• Veerman CC, Kosmidis G, Mummery CL, et al. Immaturity of human stem-cell-derived cardiomyocytes in culture: fatal flaw or soluble problem? Stem Cells Dev. 2015 May 1;24(9):1035–1052. PubMed PMID: 25583389.
   Google Scholar
• Kolanowski TJ, Antos CL, Guan K. Making human cardiomyocytes up to date: derivation, maturation state and perspectives. Int J Cardiol. 2017 Aug 15;241:379–386. PubMed PMID: 28377185.
   Google Scholar
• Sager PT, Gintant G, Turner JR, et al. Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the cardiac safety research consortium. Am Heart J. 2014 Mar;167(3):292–300. PubMed PMID: 24576511.
   Google Scholar
• Takasuna K, Asakura K, Araki S, et al. Comprehensive in vitro cardiac safety assessment using human stem cell technology: overview of CSAHi HEART initiative. J Pharmacol Toxicol Methods. 2017 Jan-Feb;83:42–54. PubMed PMID: 27646297.
   Google Scholar
• Dennis A, Wang L, Wan X, et al. hERG channel trafficking: novel targets in drug-induced long QT syndrome. Biochem Soc Trans. 2007 Nov;35(Pt 5):1060–1063. PubMed PMID: 17956279.
   Google Scholar
• Kratz JM, Schuster D, Edtbauer M, et al. Experimentally validated HERG pharmacophore models as cardiotoxicity prediction tools. J Chem Inf Model. 2014 Oct 27;54(10):2887–2901. PubMed PMID: 25148533.
   Google Scholar
• Sharma A, Burridge PW, McKeithan WL, et al. High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci Transl Med. 2017 Feb 15;9(377). PubMed PMID: 28202772; PubMed Central PMCID: PMC5409837. DOI:10.1126/scitranslmed.aaf2584
   Google Scholar
• Rana P, Anson B, Engle S, et al. Characterization of human-induced pluripotent stem cell-derived cardiomyocytes: bioenergetics and utilization in safety screening. Toxicol Sci. 2012 Nov;130(1):117–131. PubMed PMID: 22843568.
   Google Scholar
• Meseguer-Ripolles J, Khetani SR, Blanco JG, et al. Pluripotent stem cell-derived human tissue: platforms to evaluate drug metabolism and safety. AAPS J. 2017 Dec 21;20(1):20. PubMed PMID: 29270863; PubMed Central PMCID: PMC5804345.
   Google Scholar
• Mordwinkin NM, Burridge PW, Wu JC. A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards. J Cardiovasc Transl Res. 2013 Feb 6;1:22–30. PubMed PMID: 23229562; PubMed Central PMCID: PMC3556463.
   Google Scholar
• Sinnecker D, Laugwitz KL, Moretti A. Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing. Pharmacol Ther. 2014 Aug;143(2):246–252. PubMed PMID: 24657289.
   Google Scholar
• van Meer BJ, Tertoolen LG, Mummery CL. Concise review: measuring physiological responses of human pluripotent stem cell derived cardiomyocytes to drugs and disease. Stem Cells. 2016 Aug;34(8):2008–2015. PubMed PMID: 27250776; PubMed Central PMCID: PMC5113667.
   Google Scholar
• Yang X, Papoian T. Moving beyond the comprehensive in vitro proarrhythmia assay: use of human-induced pluripotent stem cell-derived cardiomyocytes to assess contractile effects associated with drug-induced structural cardiotoxicity. J Appl Toxicol. 2018 Sep;38(9):1166–1176. PubMed PMID: 29484688.
   Google Scholar
• Herron TJ. Calcium and voltage mapping in hiPSC-CM monolayers. Cell Calcium. 2016 Mar;59(2–3):84–90. PubMed PMID: 26922095.
   Google Scholar
• Dempsey GT, Chaudhary KW, Atwater N, et al. Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging. J Pharmacol Toxicol Methods. 2016 Sep-Oct;81:240–250. PubMed PMID: 27184445.
   Google Scholar
• Conant G, Lai BFL, Lu RXZ, et al. High-content assessment of cardiac function using heart-on-a-chip devices as drug screening model. Stem Cell Rev. 2017 Jun;13(3):335–346. PubMed PMID: 28429185.
   Google Scholar
• Kullak-Ublick GA, Andrade RJ, Merz M, et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut. 2017 Jun;66(6):1154–1164. PubMed PMID: 28341748; PubMed Central PMCID: PMC5532458.
   Google Scholar
• Williams DP. Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery. Philos Trans R Soc London, Ser B. 2018 Jul 5;373(1750). DOI:10.1098/rstb.2017.0228. PubMed PMID: 29786562; PubMed Central PMCID: PMC5974450.
   Google Scholar
• Cameron K, Lucendo-Villarin B, Szkolnicka D, et al. Serum-free directed differentiation of human embryonic stem cells to hepatocytes. Methods Mol Biol. 2015;1250:105–111. PubMed PMID: 26272137.
   Google Scholar
• Cameron K, Tan R, Schmidt-Heck W, et al. Recombinant laminins drive the differentiation and self-organization of hESC-derived hepatocytes. Stem Cell Reports. 2015 Dec 8;5(6):1250–1262. PubMed PMID: 26626180; PubMed Central PMCID: PMC4682209.
   Google Scholar
• Erdelyi-Belle B, Torok G, Apati A, et al. Expression of tight junction components in hepatocyte-like cells differentiated from human embryonic stem cells. Pathol Oncol Res. 2015 Sep;21(4):1059–1070. PubMed PMID: 25845432.
   Google Scholar
• Baxter M, Withey S, Harrison S, et al. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J Hepatol. 2015 Mar;62(3):581–589. PubMed PMID: 25457200; PubMed Central PMCID: PMC4334496.
   Google Scholar
• Tasnim F, Phan D, Toh YC, et al. Cost-effective differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules. Biomaterials. 2015 Nov;70:115–125. PubMed PMID: 26310107.
   Google Scholar
• Roelandt P, Pauwelyn KA, Sancho-Bru P, et al. Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells. PloS one. 2010 Aug 11;5(8):e12101. PubMed PMID: 20711405; PubMed Central PMCID: PMC2920330.
   Google Scholar
• Siller R, Greenhough S, Naumovska E, et al. Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. 2015 May 12;4(5):939–952. PubMed PMID: 25937370; PubMed Central PMCID: PMC4437467.
   Google Scholar
• Benesic A, Rahm NL, Ernst S, et al. Human monocyte-derived cells with individual hepatocyte characteristics: a novel tool for personalized in vitro studies. Lab Invest. 2012 Jun;92(6):926–936. PubMed PMID: 22469698.
   Google Scholar
• Lin C, Khetani SR. Advances in engineered liver models for investigating drug-induced liver injury. Biomed Res Int. 2016;2016:1829148. PubMed PMID: 27725933; PubMed Central PMCID: PMC5048025 in Ascendance Biotechnology (Medford, MA), which has exclusively licensed the MPCC platform from MIT for commercial pharmaceutical applications.
   Google Scholar
• Batai-Konczos A, Veres Z, Szabo M, et al. Comparative study of CYP2B1/2 induction and the transport of bilirubin and taurocholate in rat hepatocyte-mono- and hepatocyte-Kupffer cell co-cultures. J Pharmacol Toxicol Methods. 2016 Nov - Dec;82:1–8. PubMed PMID: 27235785.
   Google Scholar
• Jemnitz K, Batai-Konczos A, Szabo M, et al. A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of direct and macrophage-related effect of poly(amidoamine) dendrimers. Toxicol In Vitro. 2017 Feb;38:159–169. PubMed PMID: 27717685.
   Google Scholar
• Messner S, Agarkova I, Moritz W, et al. Multi-cell type human liver microtissues for hepatotoxicity testing. Arch Toxicol. 2013 Jan;87(1):209–213. PubMed PMID: 23143619; PubMed Central PMCID: PMC3535351.
   Google Scholar
• Nguyen TV, Ukairo O, Khetani SR, et al. Establishment of a hepatocyte-kupffer cell coculture model for assessment of proinflammatory cytokine effects on metabolizing enzymes and drug transporters. Drug Metab Dispos. 2015 May;43(5):774–785. PubMed PMID: 25739975.
   Google Scholar
• Freyer N, Greuel S, Knospel F, et al. Effects of co-culture media on hepatic differentiation of hiPSC with or without HUVEC co-culture. Int J Mol Sci. 2017 Aug 7;18(8). PubMed PMID: 28783133; PubMed Central PMCID: PMC5578114. DOI:10.3390/ijms18081724
   Google Scholar
• Ware BR, Berger DR, Khetani SR. Prediction of drug-induced liver injury in micropatterned co-cultures containing iPSC-derived human hepatocytes. Toxicol Sci. 2015 Jun;145(2):252–262. PubMed PMID: 25716675.
   Google Scholar
• Freyer N, Knospel F, Strahl N, et al. Hepatic differentiation of human induced pluripotent stem cells in a perfused three-dimensional multicompartment bioreactor. Biores Open Access. 2016;5(1):235–248. PubMed PMID: 27610270; PubMed Central PMCID: PMC5003005.
   Google Scholar
• Meier F, Freyer N, Brzeszczynska J, et al. Hepatic differentiation of human iPSCs in different 3D models: a comparative study. Int J Mol Med. 2017 Dec;40(6):1759–1771. PubMed PMID: 29039463; PubMed Central PMCID: PMC5716452.
   Google Scholar
• Underhill GH, Khetani SR. Bioengineered liver models for drug testing and cell differentiation studies. Cell Mol Gastroenterol Hepatol. 2018 Mar;5(3):426–439 e1. PubMed PMID: 29675458; PubMed Central PMCID: PMC5904032.
   Google Scholar
• Taylor CJ, Peacock S, Chaudhry AN, et al. Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types. Cell Stem Cell. 2012 Aug 3;11(2):147–152. PubMed PMID: 22862941.
   Google Scholar
• Yusa K, Rashid ST, Strick-Marchand H, et al. Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011 Oct 12;478(7369):391–394. PubMed PMID: 21993621; PubMed Central PMCID: PMC3198846.
   Google Scholar
• Chambers SM, Fasano CA, Papapetrou EP, et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009 Mar;27(3):275–280. PubMed PMID: 19252484; PubMed Central PMCID: PMC2756723.
   Google Scholar
• Karumbayaram S, Novitch BG, Patterson M, et al. Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells. 2009 Apr;27(4):806–811. PubMed PMID: 19350680; PubMed Central PMCID: PMC2895909.
   Google Scholar
• Nicholas CR, Chen J, Tang Y, et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell. 2013 May 2;12(5):573–586. PubMed PMID: 23642366; PubMed Central PMCID: PMC3699205.
   Google Scholar
• Vazin T, Ball KA, Lu H, et al. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer’s disease. Neurobiol Dis. 2014 Feb;62:62–72. PubMed PMID: 24055772; PubMed Central PMCID: PMC4122237.
   Google Scholar
• Yu DX, Di Giorgio FP, Yao J, et al. Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Reports. 2014 Mar 11;2(3):295–310. PubMed PMID: 24672753; PubMed Central PMCID: PMC3964286.
   Google Scholar
• Nguyen HX, Nekanti U, Haus DL, et al. Induction of early neural precursors and derivation of tripotent neural stem cells from human pluripotent stem cells under xeno-free conditions. J Comp Neurol. 2014 Aug 15;522(12):2767–2783. PubMed PMID: 24715528.
   Google Scholar
• Lippmann ES, Al-Ahmad A, Azarin SM, et al. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci Rep. 2014 Feb;24(4):4160. PubMed PMID: 24561821; PubMed Central PMCID: PMC3932448.
   Google Scholar
• Canfield SG, Stebbins MJ, Morales BS, et al. An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells. J Neurochem. 2017 Mar;140(6):874–888. PubMed PMID: 27935037; PubMed Central PMCID: PMC5339046.
   Google Scholar
• Singh S, Srivastava A, Kumar V, et al. Stem cells in neurotoxicology/developmental neurotoxicology: current scenario and future prospects. Mol Neurobiol. 2016 Dec;53(10):6938–6949. PubMed PMID: 26666665.
   Google Scholar
• Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol. 2016 Mar;17(3):170–182. PubMed PMID: 26818440.
   Google Scholar
• Schmidt BZ, Lehmann M, Gutbier S, et al. In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities. Arch Toxicol. 2017 Jan;91(1):1–33. PubMed PMID: 27492622.
   Google Scholar
• Rana P, Luerman G, Hess D, et al. Utilization of iPSC-derived human neurons for high-throughput drug-induced peripheral neuropathy screening. Toxicol In Vitro. 2017 Dec;45(Pt 1):111–118. PubMed PMID: 28843493.
   Google Scholar
• Jorfi M, D’Avanzo C, Kim DY, et al. Three-dimensional models of the human brain development and diseases. Adv Healthc Mater. 2018 Jan;7(1). DOI: 10.1002/adhm.201700723. PubMed PMID: 28845922; PubMed Central PMCID: PMC5762251.
   Google Scholar
• Kessler M, Hoffmann K, Brinkmann V, et al. The notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun. 2015 Dec;8(6):8989. PubMed PMID: 26643275; PubMed Central PMCID: PMC4686873.
   Google Scholar
• Lancaster MA, Renner M, Martin C-A, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013 Sep 19;501(7467):373–379. PubMed PMID: 23995685; PubMed Central PMCID: PMC3817409.
   Google Scholar
• Pasca SP. The rise of three-dimensional human brain cultures. Nature. 2018 Jan 24;553(7689):437–445. PubMed PMID: 29364288.
   Google Scholar
• Dye BR, Hill DR, Ferguson MA, et al. In vitro generation of human pluripotent stem cell derived lung organoids. eLife. 2015 Mar 24;4. DOI:10.7554/eLife.05098 PubMed PMID: 25803487; PubMed Central PMCID: PMC4370217.
   Google Scholar
• Zhong X, Gutierrez C, Xue T, et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat Commun. 2014 Jun;10(5):4047. PubMed PMID: 24915161; PubMed Central PMCID: PMC4370190.
   Google Scholar
• Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell. 2017 Dec 7;21(6):730–746 e6. PubMed PMID: 29129523.
   Google Scholar
• Leite SB, Roosens T, El Taghdouini A, et al. Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro. Biomaterials. 2016 Feb;78:1–10. PubMed PMID: 26618472.
   Google Scholar
• In JG, Foulke-Abel J, Estes MK, et al. Human mini-guts: new insights into intestinal physiology and host-pathogen interactions. Nat Clin Pract Gastroenterol Hepatol. 2016 Nov;13(11):633–642. PubMed PMID: 27677718; PubMed Central PMCID: PMC5079760.
   Google Scholar
• Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015 Jan 15;160(1–2):324–338. PubMed PMID: 25557080; PubMed Central PMCID: PMC4334572.
   Google Scholar
• Weber EJ, Chapron A, Chapron BD, et al. Development of a microphysiological model of human kidney proximal tubule function. Kidney Int. 2016 Sep;90(3):627–637. PubMed PMID: 27521113; PubMed Central PMCID: PMC4987715.
   Google Scholar
• Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017 Jan;114(1):184–194. PubMed PMID: 27399645.
   Google Scholar
• Huh D, Matthews BD, Mammoto A, et al. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25;328(5986):1662–1668. PubMed PMID: 20576885.
   Google Scholar
• Kim HJ, Li H, Collins JJ, et al. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E7–E15. PubMed PMID: 26668389; PubMed Central PMCID: PMC4711860.
   Google Scholar
• Sarkar U, Ravindra KC, Large E, et al. Integrated assessment of diclofenac biotransformation, pharmacokinetics, and omics-based toxicity in a three-dimensional human liver-immunocompetent coculture system. Drug Metab Dispos. 2017 Jul;45(7):855–866. PubMed PMID: 28450578; PubMed Central PMCID: PMC5469400.
   Google Scholar
• Fernandez CE, Yen RW, Perez SM, et al. Human vascular microphysiological system for in vitro drug screening. Sci Rep. 2016 Feb;18(6):21579. PubMed PMID: 26888719; PubMed Central PMCID: PMC4757887.
   Google Scholar
• Tsamandouras N, Chen WLK, Edington CD, et al. Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. AAPS J. 2017 Sep;19(5):1499–1512. PubMed PMID: 28752430.
   Google Scholar
• Miller PG, Shuler ML. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol Bioeng. 2016 Oct;113(10):2213–2227. PubMed PMID: 27070809.
   Google Scholar
• Maass C, Stokes CL, Griffith LG, et al. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integr Biol (Camb). 2017 Apr 18;9(4):290–302. PubMed PMID: 28267162; PubMed Central PMCID: PMC5729907.
   Google Scholar
• Oleaga C, Bernabini C, Smith AS, et al. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep. 2016 Feb;3(6):20030. PubMed PMID: 26837601; PubMed Central PMCID: PMC4738272.
   Google Scholar
• Bader BM, Steder A, Klein AB, et al. Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings. PloS one. 2017;12(10):e0186147. PubMed PMID: 29028808; PubMed Central PMCID: PMC5640229.
   Google Scholar
• Hong HJ, Koom WS, Koh WG. Cell microarray technologies for high-throughput cell-based biosensors. Sensors. 2017 Jun 5;17(6). PubMed PMID: 28587242; PubMed Central PMCID: PMC5492771. DOI:10.3390/s17061293
   Google Scholar
• Pasca AM, Sloan SA, Clarke LE, et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015 Jul;12(7):671–678. PubMed PMID: 26005811; PubMed Central PMCID: PMC4489980.
   Google Scholar