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

Polonchuk, L; Chabria, M; Badi, L; Hoflack, J-C; Figtree, G; Davies, MJ; Gentile, C

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

Polonchuk, L Chabria, M Badi, L Hoflack, J-C Figtree, G Davies, MJ Gentile, C

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Publisher:: Nature Publishing Group
Publication Type:: Journal Article
Citation:: Scientific Reports, 2017, 7, (1), pp. 1-12
Issue Date:: 2017-08-01

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Field	Value	Language
dc.contributor.author	Polonchuk, L
dc.contributor.author	Chabria, M
dc.contributor.author	Badi, L
dc.contributor.author	Hoflack, J-C
dc.contributor.author	Figtree, G
dc.contributor.author	Davies, MJ
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.date.accessioned	2022-08-25T06:32:59Z
dc.date.available	2017-06-26
dc.date.available	2022-08-25T06:32:59Z
dc.date.issued	2017-08-01
dc.identifier.citation	Scientific Reports, 2017, 7, (1), pp. 1-12
dc.identifier.issn	2045-2322
dc.identifier.issn	2045-2322
dc.identifier.uri	http://hdl.handle.net/10453/160847
dc.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.
dc.format	Electronic
dc.language	eng
dc.publisher	Nature Publishing Group
dc.relation.ispartof	Scientific Reports
dc.relation.isbasedon	10.1038/s41598-017-06385-8
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cell Survival
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Heart
dc.subject.mesh	Humans
dc.subject.mesh	Models, Biological
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cell Survival
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Heart
dc.subject.mesh	Humans
dc.subject.mesh	Models, Biological
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Heart
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Humans
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cell Survival
dc.subject.mesh	Models, Biological
dc.title	Cardiac spheroids as promising in vitro models to study the human heart microenvironment.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-08-25T06:32:52Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	7
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/160847