Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure
Introduction: Myocardial recovery is one of the targets for heart failure treatment. A non-negligible number of heart failure with reduced ejection fraction (EF) patients experience myocardial recovery through treatment. Although myocardial hypoxia has been reported to contribute to the progression...
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doaj-7e6337f124da43369f97d4d7d9354f742021-04-12T04:24:05ZengElsevierRegenerative Therapy2352-32042021-12-01186675Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failureYu Yamasaki0Katsuhisa Matsuura1Daisuke Sasaki2Tatsuya Shimizu3Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, JapanInstitute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan; Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan; Corresponding author. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, JapanInstitute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, JapanIntroduction: Myocardial recovery is one of the targets for heart failure treatment. A non-negligible number of heart failure with reduced ejection fraction (EF) patients experience myocardial recovery through treatment. Although myocardial hypoxia has been reported to contribute to the progression of heart failure even in non-ischemic cardiomyopathy, the relationship between contractile recovery and re-oxygenation and its underlying mechanisms remain unclear. The present study investigated the effects of hypoxia/re-oxygenation on bioengineered cardiac cell sheets-tissue function and the underlying mechanisms. Methods: Bioengineered cardiac cell sheets-tissue was fabricated with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) using temperature-responsive culture dishes. Cardiac tissue functions in the following conditions were evaluated with a contractile force measurement system: continuous normoxia (20% O2) for 12 days; hypoxia (1% O2) for 4 days followed by normoxia (20% O2) for 8 days; or continuous hypoxia (1% O2) for 8 days. Cell number, sarcomere structure, ATP levels, mRNA expressions and Ca2+ transients of hiPSC-CM in those conditions were also assessed. Results: Hypoxia (4 days) elicited progressive decreases in contractile force, maximum contraction velocity, maximum relaxation velocity, Ca2+ transient amplitude and ATP level, but sarcomere structure and cell number were not affected. Re-oxygenation (8 days) after hypoxia (4 days) was associated with progressive increases in contractile force, maximum contraction velocity and relaxation time to the similar extent levels of continuous normoxia group, while maximum relaxation velocity was still significantly low even after re-oxygenation. Ca2+ transient magnitude, cell number, sarcomere structure and ATP level after re-oxygenation were similar to those in the continuous normoxia group. Hypoxia/re-oxygenation up-regulated mRNA expression of PLN. Conclusions: Hypoxia and re-oxygenation condition directly affected human bioengineered cardiac tissue function. Further understanding the molecular mechanisms of functional recovery of cardiac tissue after re-oxygenation might provide us the new insight on heart failure with recovered ejection fraction and preserved ejection fraction.http://www.sciencedirect.com/science/article/pii/S2352320421000274Human induced pluripotent stem cellsCardiac cell sheetContractile forceHypoxiaRe-oxygenationHeart failure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Yamasaki Katsuhisa Matsuura Daisuke Sasaki Tatsuya Shimizu |
spellingShingle |
Yu Yamasaki Katsuhisa Matsuura Daisuke Sasaki Tatsuya Shimizu Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure Regenerative Therapy Human induced pluripotent stem cells Cardiac cell sheet Contractile force Hypoxia Re-oxygenation Heart failure |
author_facet |
Yu Yamasaki Katsuhisa Matsuura Daisuke Sasaki Tatsuya Shimizu |
author_sort |
Yu Yamasaki |
title |
Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
title_short |
Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
title_full |
Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
title_fullStr |
Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
title_full_unstemmed |
Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
title_sort |
assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure |
publisher |
Elsevier |
series |
Regenerative Therapy |
issn |
2352-3204 |
publishDate |
2021-12-01 |
description |
Introduction: Myocardial recovery is one of the targets for heart failure treatment. A non-negligible number of heart failure with reduced ejection fraction (EF) patients experience myocardial recovery through treatment. Although myocardial hypoxia has been reported to contribute to the progression of heart failure even in non-ischemic cardiomyopathy, the relationship between contractile recovery and re-oxygenation and its underlying mechanisms remain unclear. The present study investigated the effects of hypoxia/re-oxygenation on bioengineered cardiac cell sheets-tissue function and the underlying mechanisms. Methods: Bioengineered cardiac cell sheets-tissue was fabricated with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) using temperature-responsive culture dishes. Cardiac tissue functions in the following conditions were evaluated with a contractile force measurement system: continuous normoxia (20% O2) for 12 days; hypoxia (1% O2) for 4 days followed by normoxia (20% O2) for 8 days; or continuous hypoxia (1% O2) for 8 days. Cell number, sarcomere structure, ATP levels, mRNA expressions and Ca2+ transients of hiPSC-CM in those conditions were also assessed. Results: Hypoxia (4 days) elicited progressive decreases in contractile force, maximum contraction velocity, maximum relaxation velocity, Ca2+ transient amplitude and ATP level, but sarcomere structure and cell number were not affected. Re-oxygenation (8 days) after hypoxia (4 days) was associated with progressive increases in contractile force, maximum contraction velocity and relaxation time to the similar extent levels of continuous normoxia group, while maximum relaxation velocity was still significantly low even after re-oxygenation. Ca2+ transient magnitude, cell number, sarcomere structure and ATP level after re-oxygenation were similar to those in the continuous normoxia group. Hypoxia/re-oxygenation up-regulated mRNA expression of PLN. Conclusions: Hypoxia and re-oxygenation condition directly affected human bioengineered cardiac tissue function. Further understanding the molecular mechanisms of functional recovery of cardiac tissue after re-oxygenation might provide us the new insight on heart failure with recovered ejection fraction and preserved ejection fraction. |
topic |
Human induced pluripotent stem cells Cardiac cell sheet Contractile force Hypoxia Re-oxygenation Heart failure |
url |
http://www.sciencedirect.com/science/article/pii/S2352320421000274 |
work_keys_str_mv |
AT yuyamasaki assessmentofhumanbioengineeredcardiactissuefunctioninhypoxicandreoxygenizedenvironmentstounderstandfunctionalrecoveryinheartfailure AT katsuhisamatsuura assessmentofhumanbioengineeredcardiactissuefunctioninhypoxicandreoxygenizedenvironmentstounderstandfunctionalrecoveryinheartfailure AT daisukesasaki assessmentofhumanbioengineeredcardiactissuefunctioninhypoxicandreoxygenizedenvironmentstounderstandfunctionalrecoveryinheartfailure AT tatsuyashimizu assessmentofhumanbioengineeredcardiactissuefunctioninhypoxicandreoxygenizedenvironmentstounderstandfunctionalrecoveryinheartfailure |
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