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Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping

Current drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent s...

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Autores principales: Gunawan, Marvin G., Sangha, Sarabjit S., Shafaattalab, Sanam, Lin, Eric, Heims‐Waldron, Danielle A., Bezzerides, Vassilios J., Laksman, Zachary, Tibbits, Glen F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780813/
https://www.ncbi.nlm.nih.gov/pubmed/32927497
http://dx.doi.org/10.1002/sctm.19-0440
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author Gunawan, Marvin G.
Sangha, Sarabjit S.
Shafaattalab, Sanam
Lin, Eric
Heims‐Waldron, Danielle A.
Bezzerides, Vassilios J.
Laksman, Zachary
Tibbits, Glen F.
author_facet Gunawan, Marvin G.
Sangha, Sarabjit S.
Shafaattalab, Sanam
Lin, Eric
Heims‐Waldron, Danielle A.
Bezzerides, Vassilios J.
Laksman, Zachary
Tibbits, Glen F.
author_sort Gunawan, Marvin G.
collection PubMed
description Current drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell‐derived atrial and ventricular cardiomyocytes (hiPSC‐aCMs and hiPSC‐vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial‐selective compounds in vitro. We optimized differentiation of hiPSC‐aCMs by modulating the WNT and retinoid signaling pathways. Characterization of the transcriptome and proteome revealed that retinoic acid pushes the differentiation process into the atrial lineage and generated hiPSC‐aCMs. Functional characterization using optical mapping showed that hiPSC‐aCMs have shorter action potential durations and faster Ca(2+) handling dynamics compared with hiPSC‐vCMs. Furthermore, pharmacological investigation of hiPSC‐aCMs captured atrial‐selective effects by displaying greater sensitivity to atrial‐selective compounds 4‐aminopyridine, AVE0118, UCL1684, and vernakalant when compared with hiPSC‐vCMs. These results established that a model system incorporating hiPSC‐aCMs combined with optical mapping is well‐suited for preclinical drug screening of novel and targeted atrial selective compounds.
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spelling pubmed-77808132021-01-08 Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping Gunawan, Marvin G. Sangha, Sarabjit S. Shafaattalab, Sanam Lin, Eric Heims‐Waldron, Danielle A. Bezzerides, Vassilios J. Laksman, Zachary Tibbits, Glen F. Stem Cells Transl Med Cell‐based Drug Development, Screening, and Toxicology Current drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell‐derived atrial and ventricular cardiomyocytes (hiPSC‐aCMs and hiPSC‐vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial‐selective compounds in vitro. We optimized differentiation of hiPSC‐aCMs by modulating the WNT and retinoid signaling pathways. Characterization of the transcriptome and proteome revealed that retinoic acid pushes the differentiation process into the atrial lineage and generated hiPSC‐aCMs. Functional characterization using optical mapping showed that hiPSC‐aCMs have shorter action potential durations and faster Ca(2+) handling dynamics compared with hiPSC‐vCMs. Furthermore, pharmacological investigation of hiPSC‐aCMs captured atrial‐selective effects by displaying greater sensitivity to atrial‐selective compounds 4‐aminopyridine, AVE0118, UCL1684, and vernakalant when compared with hiPSC‐vCMs. These results established that a model system incorporating hiPSC‐aCMs combined with optical mapping is well‐suited for preclinical drug screening of novel and targeted atrial selective compounds. John Wiley & Sons, Inc. 2020-09-14 /pmc/articles/PMC7780813/ /pubmed/32927497 http://dx.doi.org/10.1002/sctm.19-0440 Text en © 2020 The Authors. stem cells translational medicine published by Wiley Periodicals LLC on behalf of AlphaMed Press. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cell‐based Drug Development, Screening, and Toxicology
Gunawan, Marvin G.
Sangha, Sarabjit S.
Shafaattalab, Sanam
Lin, Eric
Heims‐Waldron, Danielle A.
Bezzerides, Vassilios J.
Laksman, Zachary
Tibbits, Glen F.
Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title_full Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title_fullStr Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title_full_unstemmed Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title_short Drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
title_sort drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and optical mapping
topic Cell‐based Drug Development, Screening, and Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780813/
https://www.ncbi.nlm.nih.gov/pubmed/32927497
http://dx.doi.org/10.1002/sctm.19-0440
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