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Automated image analysis system for studying cardiotoxicity in human pluripotent stem cell-Derived cardiomyocytes

Lu Cao, Andries D. van der Meer, Fons J. Verbeek, Robert Passier
2020 BMC Bioinformatics  
Alternatively, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show great potential for disease modelling and drug-induced toxicity screenings.  ...  In this paper, we report on the development of a fully automated image analysis system for quantification of cardiotoxic phenotypes from hiPSC-CMs that are treated with various concentrations of anticancer  ...  The reprogramming of human somatic cells to induced pluripotent stem cells (hiPSC) was described for the first time in 2007 [7] .  ... 
doi:10.1186/s12859-020-3466-1 pmid:32408861 fatcat:2sfu4de6lndonlci63sdv4jtfa

High Throughput Image Analysis for Cardiotoxicity Study using Human Pluripotent Stem Cell-Derived Cardiomyocytes

2020 Journal of Cellular Immunology  
To that end, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming promising and important for disease modeling and drug-induced toxicity screening.  ...  This fully automated image analysis system is dedicated to analyze high-throughput images and is capable of determining cardiotoxicity based on phenotypic changes in hiPSC-CMs.  ...  We designed a fully automated image analysis system [8] for cardiotoxicity analysis.  ... 
doi:10.33696/immunology.2.062 fatcat:pkisxlfx6zcgdcgaphx575a2ey

Pluripotent Stem Cell-Derived Human Tissue: Platforms to Evaluate Drug Metabolism and Safety

Jose Meseguer-Ripolles, Salman R. Khetani, Javier G. Blanco, Mairi Iredale, David C. Hay
2017 AAPS Journal  
We believe that the recent advances in production of stem cell-derived hepatocytes and cardiomyocytes combined with cutting-edge engineering technologies make them an attractive alternative to current  ...  Recently, stem cell technology has shown promise in drug development and has been proposed as an alternative to current industrial systems.  ...  Stem cell-derived hepatocytes and cardiomyocytes have been used successfully to study drug metabolism on defined genetic backgrounds, providing critical proof of concept that pluripotent stem cell-derived  ... 
doi:10.1208/s12248-017-0171-8 pmid:29270863 pmcid:PMC5804345 fatcat:pxdicmsow5glho27ccblnbhys4

Assessment of Cardiotoxicity With Stem Cell-Based Strategies

Aaltje Maria Stella Stoter, Marc N. Hirt, Justus Stenzig, Florian Weinberger
2020 Clinical Therapeutics  
Current differentiation protocols allow for the generation of human pluripotent stem cell-derived cardiomyocytes in basically unlimited numbers and offer the opportunity to study drug effects on human  ...  Pluripotent stem cell-derived cardiomyocytes have the potential to substantially change how preclinical cardiotoxicity screening is performed.  ...  Whereas many organs harbor a stem/progenitor cell population, the heart lacks such a stem/progenitor cell population, 43 and the only source for a large number of human cardiomyocytes are pluripotent  ... 
doi:10.1016/j.clinthera.2020.08.012 pmid:32938533 fatcat:j5en23sr7rhi5ie2h2m7xkzmcq

Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

Oksana Sirenko, Evan F. Cromwell, Carole Crittenden, Jessica A. Wignall, Fred A. Wright, Ivan Rusyn
2013 Toxicology and Applied Pharmacology  
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development.  ...  Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates  ...  Acknowledgments This work was supported, in part, by the National Institutes of Health [ES015241 to I.R.]; and the United States Environmental Protection Agency [STAR RD83516601 to I.R.].  ... 
doi:10.1016/j.taap.2013.09.017 pmid:24095675 pmcid:PMC3900303 fatcat:b6nn7hhaxfge7fks5hbeyw2xpy

Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing

Daniel Sinnecker, Karl-Ludwig Laugwitz, Alessandra Moretti
2014 Pharmacology and Therapeutics  
Induced pluripotent stem cell (iPSC) technology is creating exciting new opportunities for cardiovascular research by providing platforms to study the mechanisms of disease pathogenesis that could lead  ...  In this review, the potential usefulness of iPSC-derived cardiomyocytes in drug development as well as in drug toxicity testing is discussed, with a focus on the achievements that have been already made  ...  for the research.  ... 
doi:10.1016/j.pharmthera.2014.03.004 pmid:24657289 fatcat:4bmzd67vgvclvf7y74iccas6sy

Human Pluripotent Stem Cell Applications in Drug Discovery and Toxicology – An overview [chapter]

Shiva Prasad Potta, Tomo Šarić, Michael Heke, Harinath Bahudhanapati, Jürgen Hescheler
2014 Pluripotent Stem Cell Biology - Advances in Mechanisms, Methods and Models  
Acknowledgements The work in the author s laboratories is supported by the European Union FP Program, "undesministerium f(r "ildung und Forschung "M"F , Else-Kröner-Fresenius Stiftung, Excellence Research  ...  Cardiotoxicity testing using pluripotent stem cell-derived human cardiomyocytes and state-of-the-art bioanalytics a review.  ...  The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells.  ... 
doi:10.5772/58485 fatcat:56jrvbhgvzh5dfxj3ctw2lvika

Will iPSC-cardiomyocytes revolutionize the discovery of drugs for heart disease?

Arne AN Bruyneel, Wesley L McKeithan, Dries AM Feyen, Mark Mercola
2018 Current opinion in pharmacology (Print)  
The advent of human induced pluripotent stem cells and the ability to make limitless numbers of cardiomyocytes could revolutionize heart disease modeling and drug discovery.  ...  Keywords pluripotent stem cells; cardiovascular disease; toxicity screening; drug discovery Bruyneel et al.  ...  An exciting new paradigm in cardiovascular drug discovery is the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) and vascular cells to create in vitro models of human  ... 
doi:10.1016/j.coph.2018.07.003 pmid:30081259 pmcid:PMC6261432 fatcat:bzau63qgyrhqfnvu3oysydm6eq

Considerations in designing systems for large scale production of human cardiomyocytes from pluripotent stem cells

Allen Chen, Sherwin Ting, Jasmin Seow, Shaul Reuveny, Steve Oh
2014 Stem Cell Research & Therapy  
Human pluripotent stem cell (hPSC)-derived cardiomyocytes have attracted attention as an unlimited source of cells for cardiac therapies.  ...  in their infancy but can also generate high cardiomyocyte yields.  ...  Figure 1 1 Bioprocessing of human pluripotent stem cell-derived cardiomyocytes.  ... 
doi:10.1186/scrt401 pmid:24444355 pmcid:PMC4055057 fatcat:fdgtt7qrw5bvhfw6roqilpcm2m

A Review of Human Pluripotent Stem Cell-Derived Cardiomyocytes for High-Throughput Drug Discovery, Cardiotoxicity Screening, and Publication Standards

Nicholas M. Mordwinkin, Paul W. Burridge, Joseph C. Wu
2012 Journal of Cardiovascular Translational Research  
The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling,  ...  In this review, we discuss the use of pluripotent stem cell-derived cardiomyocytes for drug discovery and cardiotoxicity screening, as well as current hurdles that must be overcome for wider clinical applications  ...  In contrast to potential therapeutic engraftment studies, the use of human pluripotent stem cell-derived CMs for drug discovery and screening has already proven promising, as hiPSC-CMs have been shown  ... 
doi:10.1007/s12265-012-9423-2 pmid:23229562 pmcid:PMC3556463 fatcat:qxd7waiqffg7nfbd33ka6k6r2e

A Novel High-Content Screening-Based Method for Anti-Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Diogo Crispim Nascimento Portella, Erik Aranha Rossi, Bruno Diaz Paredes, Tanira Matutino Bastos, Cássio Santana Meira, Carolina Vasques Kymie Nonaka, Daniela Nascimento Silva, Alex Improta-Caria, Diogo Rodrigo Magalhaes Moreira, Ana Cristina Lima Leite, Gevanio Bezerra de Oliveira Filho, José Maria Barbosa Filho (+4 others)
2021 Stem Cells International  
Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) have the potential to accelerate the process of drug discovery for Chagas disease, through predictive preclinical assays in  ...  Automated multiparametric analyses were performed using an automated high-content imaging system.  ...  Acknowledgments This study was supported with grants from CNPq, FAPESB, and FINEP. The authors thank Ms. Roquelina Assis for technical support. Supplementary Materials  ... 
doi:10.1155/2021/2642807 fatcat:7kecptur7zfmrh6yifl45qlidm

Comparative Gene Expression Profiling in Human-Induced Pluripotent Stem Cell—Derived Cardiocytes and Human and Cynomolgus Heart Tissue

Dinesh Puppala, Leon P. Collis, Sunny Z. Sun, Vinicius Bonato, Xian Chen, Blake Anson, Mathew Pletcher, Bernard Fermini, Sandra J. Engle
2012 Toxicological Sciences  
These results suggest that stem cell-derived cardiocytes may represent a novel in vitro model to study human cardiac toxicity with potential ex vivo and in vivo translation.  ...  Here we describe the gene expression profile of human-induced pluripotent stem cell-derived cardiocytes (iCC) postthaw over a period of 42 days in culture and compare this profile to human fetal and adult  ...  Cardiocytes derived from human pluripotent stem cells offer a promising opportunity to evaluate cardiotoxicity associated with direct, intrinsic effects on cardiomyocytes.  ... 
doi:10.1093/toxsci/kfs282 pmid:22982684 fatcat:mmofxpbahbhvbcqo45dwuftsry

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells

Oksana Sirenko, Carole Crittenden, Nick Callamaras, Jayne Hesley, Yen-Wen Chen, Carlos Funes, Ivan Rusyn, Blake Anson, Evan F. Cromwell
2013 Journal of Biomolecular Screening  
Human cardiomyocytes derived from stem cell sources offer more clinically relevant cell-based models than those presently available.  ...  Human-induced pluripotent stem cell-derived cardiomyocytes are especially attractive because they express ion channels and demonstrate spontaneous mechanical and electrical activity similar to adult cardiomyocytes  ...  Funding The authors received no financial support for the research, authorship, and/or publication of this article.  ... 
doi:10.1177/1087057112457590 pmid:22972846 fatcat:wcaegwccbzedrgcrkqhxb4sfom

A human 3D myocardial microtissue model for cardiotoxicity testing

Philippe Beauchamp, Irina Agarkova, Wolfgang Moritz, Jens Kelm, Christian Zuppinger
2013 Toxicology Letters  
Technology Morphology and protein expression Conclusion • IPSC-derived human cardiomyocytes (iCell cardiomyocytes, CDI) show a highly differentiated cytoskeleton with sarcomeres, expression of tissue-specific  ...  proteins and spontaneous contractile activity in 2D culture  ...  Hence, an in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSC) from human origin was developed and characterized.  ... 
doi:10.1016/j.toxlet.2013.05.268 fatcat:5scvdgxzvzgpxp4hmlgtowebza

A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing

Heinz-Georg Jahnke, Daniella Steel, Stephan Fleischer, Diana Seidel, Randy Kurz, Silvia Vinz, Kerstin Dahlenborg, Peter Sartipy, Andrea A. Robitzki, Yao Liang Tang
2013 PLoS ONE  
To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing  ...  In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity.  ...  stem cell derived hCMC forward to reliable longterm in vitro cardiotoxicity testing.  ... 
doi:10.1371/journal.pone.0068971 pmid:23861955 pmcid:PMC3704625 fatcat:vhmb6aso2rb3bp7my65mkdjwvq
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