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Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are expected to play an important role in heart therapies, in which hiPSC-CMs should generate sufficient contractile force to pump blood. However, recent studies have shown that the contractility of myocardial mimics compos...

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Autores principales: Mizutani, Takeomi, Furusawa, Kazuya, Haga, Hisashi, Kawabata, Kazushige
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society for Regenerative Medicine 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581838/
https://www.ncbi.nlm.nih.gov/pubmed/31245478
http://dx.doi.org/10.1016/j.reth.2016.02.009
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author Mizutani, Takeomi
Furusawa, Kazuya
Haga, Hisashi
Kawabata, Kazushige
author_facet Mizutani, Takeomi
Furusawa, Kazuya
Haga, Hisashi
Kawabata, Kazushige
author_sort Mizutani, Takeomi
collection PubMed
description Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are expected to play an important role in heart therapies, in which hiPSC-CMs should generate sufficient contractile force to pump blood. However, recent studies have shown that the contractility of myocardial mimics composed of hiPSC-CMs is lower than that of adult human myocardium. To examine the mechanism by which contractile force output of hiPSC-CMs is weakened, we measured the contractile force of single hiPSC-CMs and observed the fibrous distribution of myosin II regulatory light chain (MRLC) of cardiac (contributes to beating) and non-cardiac (does not contribute to beating) isoforms. Single hiPSC-CMs were cultured on an extracellular matrix gel, and the contractile force and strain energy exerted on the gel were measured. Strain energy was not uniform between cells and ranged from 0.2 to 5.8 pJ. The combination of contractile force measurement and immunofluorescent microscopy for MRLC isoforms showed that cells with higher strain energy expressed the weakened non-cardiac myosin II fibers compared to those of cells with lower strain energy. Observation of cardiac and non-cardiac MRLC showed that the MRLC isoforms formed heterogeneous filament networks. These results suggest that strain energy output from single hiPSC-CMs depends both cardiac and non-cardiac myosin fibers, which prevent deformation of the cell body.
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spelling pubmed-65818382019-06-26 Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells Mizutani, Takeomi Furusawa, Kazuya Haga, Hisashi Kawabata, Kazushige Regen Ther Original Article Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are expected to play an important role in heart therapies, in which hiPSC-CMs should generate sufficient contractile force to pump blood. However, recent studies have shown that the contractility of myocardial mimics composed of hiPSC-CMs is lower than that of adult human myocardium. To examine the mechanism by which contractile force output of hiPSC-CMs is weakened, we measured the contractile force of single hiPSC-CMs and observed the fibrous distribution of myosin II regulatory light chain (MRLC) of cardiac (contributes to beating) and non-cardiac (does not contribute to beating) isoforms. Single hiPSC-CMs were cultured on an extracellular matrix gel, and the contractile force and strain energy exerted on the gel were measured. Strain energy was not uniform between cells and ranged from 0.2 to 5.8 pJ. The combination of contractile force measurement and immunofluorescent microscopy for MRLC isoforms showed that cells with higher strain energy expressed the weakened non-cardiac myosin II fibers compared to those of cells with lower strain energy. Observation of cardiac and non-cardiac MRLC showed that the MRLC isoforms formed heterogeneous filament networks. These results suggest that strain energy output from single hiPSC-CMs depends both cardiac and non-cardiac myosin fibers, which prevent deformation of the cell body. Japanese Society for Regenerative Medicine 2016-03-22 /pmc/articles/PMC6581838/ /pubmed/31245478 http://dx.doi.org/10.1016/j.reth.2016.02.009 Text en © 2016, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Mizutani, Takeomi
Furusawa, Kazuya
Haga, Hisashi
Kawabata, Kazushige
Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title_full Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title_fullStr Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title_full_unstemmed Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title_short Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
title_sort heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581838/
https://www.ncbi.nlm.nih.gov/pubmed/31245478
http://dx.doi.org/10.1016/j.reth.2016.02.009
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