Cardiac spheroids as promising in vitro models to study the human heart microenvironment

Abstract Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial ce...

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Autores principales:	Liudmila Polonchuk, Mamta Chabria, Laura Badi, Jean-Christophe Hoflack, Gemma Figtree, Michael J. Davies, Carmine Gentile
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/041130723354477b9dc45e4c88195335
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spelling	oai:doaj.org-article:041130723354477b9dc45e4c881953352021-12-02T16:06:19ZCardiac spheroids as promising in vitro models to study the human heart microenvironment10.1038/s41598-017-06385-82045-2322https://doaj.org/article/041130723354477b9dc45e4c881953352017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06385-8https://doaj.org/toc/2045-2322Abstract Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present in vivo. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate dose-dependent cytotoxic effects, which are inhibited by the nitric oxide synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS, implicating peroxynitrous acid as a key damaging agent. These data indicate that CSs mimic important features of human heart morphology, biochemistry and pharmacology in vitro, offering a promising alternative to animals and standard cell cultures with regard to mechanistic insights and prediction of toxic effects in human heart tissue.Liudmila PolonchukMamta ChabriaLaura BadiJean-Christophe HoflackGemma FigtreeMichael J. DaviesCarmine GentileNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liudmila Polonchuk Mamta Chabria Laura Badi Jean-Christophe Hoflack Gemma Figtree Michael J. Davies Carmine Gentile Cardiac spheroids as promising in vitro models to study the human heart microenvironment
description	Abstract Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present in vivo. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate dose-dependent cytotoxic effects, which are inhibited by the nitric oxide synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS, implicating peroxynitrous acid as a key damaging agent. These data indicate that CSs mimic important features of human heart morphology, biochemistry and pharmacology in vitro, offering a promising alternative to animals and standard cell cultures with regard to mechanistic insights and prediction of toxic effects in human heart tissue.
format	article
author	Liudmila Polonchuk Mamta Chabria Laura Badi Jean-Christophe Hoflack Gemma Figtree Michael J. Davies Carmine Gentile
author_facet	Liudmila Polonchuk Mamta Chabria Laura Badi Jean-Christophe Hoflack Gemma Figtree Michael J. Davies Carmine Gentile
author_sort	Liudmila Polonchuk
title	Cardiac spheroids as promising in vitro models to study the human heart microenvironment
title_short	Cardiac spheroids as promising in vitro models to study the human heart microenvironment
title_full	Cardiac spheroids as promising in vitro models to study the human heart microenvironment
title_fullStr	Cardiac spheroids as promising in vitro models to study the human heart microenvironment
title_full_unstemmed	Cardiac spheroids as promising in vitro models to study the human heart microenvironment
title_sort	cardiac spheroids as promising in vitro models to study the human heart microenvironment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/041130723354477b9dc45e4c88195335
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Cardiac spheroids as promising in vitro models to study the human heart microenvironment

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