Human induced pluripotent stem cell-based platform for modeling cardiac ischemia

Abstract Ischemic heart disease is a major cause of death worldwide, and the only available therapy to salvage the tissue is reperfusion, which can initially cause further damage. Many therapeutics that have been promising in animal models have failed in human trials. Thus, functional human based ca...

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Autores principales:	Martta Häkli, Joose Kreutzer, Antti-Juhana Mäki, Hannu Välimäki, Henna Lappi, Heini Huhtala, Pasi Kallio, Katriina Aalto-Setälä, Mari Pekkanen-Mattila
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4b8f6361442485f8e2228b64c1c0b3a
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spelling	oai:doaj.org-article:a4b8f6361442485f8e2228b64c1c0b3a2021-12-02T12:11:34ZHuman induced pluripotent stem cell-based platform for modeling cardiac ischemia10.1038/s41598-021-83740-w2045-2322https://doaj.org/article/a4b8f6361442485f8e2228b64c1c0b3a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83740-whttps://doaj.org/toc/2045-2322Abstract Ischemic heart disease is a major cause of death worldwide, and the only available therapy to salvage the tissue is reperfusion, which can initially cause further damage. Many therapeutics that have been promising in animal models have failed in human trials. Thus, functional human based cardiac ischemia models are required. In this study, a human induced pluripotent stem cell derived-cardiomyocyte (hiPSC-CM)-based platform for modeling ischemia–reperfusion was developed utilizing a system enabling precise control over oxygen concentration and real-time monitoring of the oxygen dynamics as well as iPS-CM functionality. In addition, morphology and expression of hypoxia-related genes and proteins were evaluated as hiPSC-CM response to 8 or 24 h hypoxia and 24 h reoxygenation. During hypoxia, initial decrease in hiPSC-CM beating frequency was observed, after which the CMs adapted to the conditions and the beating frequency gradually increased already before reoxygenation. During reoxygenation, the beating frequency typically first surpassed the baseline before settling down to the values close the baseline. Furthermore, slowing on the field potential propagation throughout the hiPSC-CM sheet as well as increase in depolarization time and decrease in overall field potential duration were observed during hypoxia. These changes were reversed during reoxygenation. Disorganization of sarcomere structures was observed after hypoxia and reoxygenation, supported by decrease in the expression of sarcomeric proteins. Furthermore, increase in the expression of gene encoding glucose transporter 1 was observed. These findings indicate, that despite their immature phenotype, hiPSC-CMs can be utilized in modeling ischemia–reperfusion injury.Martta HäkliJoose KreutzerAntti-Juhana MäkiHannu VälimäkiHenna LappiHeini HuhtalaPasi KallioKatriina Aalto-SetäläMari Pekkanen-MattilaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martta Häkli Joose Kreutzer Antti-Juhana Mäki Hannu Välimäki Henna Lappi Heini Huhtala Pasi Kallio Katriina Aalto-Setälä Mari Pekkanen-Mattila Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
description	Abstract Ischemic heart disease is a major cause of death worldwide, and the only available therapy to salvage the tissue is reperfusion, which can initially cause further damage. Many therapeutics that have been promising in animal models have failed in human trials. Thus, functional human based cardiac ischemia models are required. In this study, a human induced pluripotent stem cell derived-cardiomyocyte (hiPSC-CM)-based platform for modeling ischemia–reperfusion was developed utilizing a system enabling precise control over oxygen concentration and real-time monitoring of the oxygen dynamics as well as iPS-CM functionality. In addition, morphology and expression of hypoxia-related genes and proteins were evaluated as hiPSC-CM response to 8 or 24 h hypoxia and 24 h reoxygenation. During hypoxia, initial decrease in hiPSC-CM beating frequency was observed, after which the CMs adapted to the conditions and the beating frequency gradually increased already before reoxygenation. During reoxygenation, the beating frequency typically first surpassed the baseline before settling down to the values close the baseline. Furthermore, slowing on the field potential propagation throughout the hiPSC-CM sheet as well as increase in depolarization time and decrease in overall field potential duration were observed during hypoxia. These changes were reversed during reoxygenation. Disorganization of sarcomere structures was observed after hypoxia and reoxygenation, supported by decrease in the expression of sarcomeric proteins. Furthermore, increase in the expression of gene encoding glucose transporter 1 was observed. These findings indicate, that despite their immature phenotype, hiPSC-CMs can be utilized in modeling ischemia–reperfusion injury.
format	article
author	Martta Häkli Joose Kreutzer Antti-Juhana Mäki Hannu Välimäki Henna Lappi Heini Huhtala Pasi Kallio Katriina Aalto-Setälä Mari Pekkanen-Mattila
author_facet	Martta Häkli Joose Kreutzer Antti-Juhana Mäki Hannu Välimäki Henna Lappi Heini Huhtala Pasi Kallio Katriina Aalto-Setälä Mari Pekkanen-Mattila
author_sort	Martta Häkli
title	Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
title_short	Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
title_full	Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
title_fullStr	Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
title_full_unstemmed	Human induced pluripotent stem cell-based platform for modeling cardiac ischemia
title_sort	human induced pluripotent stem cell-based platform for modeling cardiac ischemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a4b8f6361442485f8e2228b64c1c0b3a
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Human induced pluripotent stem cell-based platform for modeling cardiac ischemia

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