Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis.

Figtree, GA; Bubb, KJ; Tang, O; Kizana, E; Gentile, C

Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis.

Figtree, GA Bubb, KJ Tang, O Kizana, E Gentile, C

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Publisher:: Karger Publishers
Publication Type:: Journal Article
Citation:: Cells, Tissues, Organs: in vivo, in vitro, 2017, 204, (3-4), pp. 191-198
Issue Date:: 2017

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Field	Value	Language
dc.contributor.author	Figtree, GA
dc.contributor.author	Bubb, KJ
dc.contributor.author	Tang, O
dc.contributor.author	Kizana, E
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.date.accessioned	2022-08-25T06:28:07Z
dc.date.available	2017-05-11
dc.date.available	2022-08-25T06:28:07Z
dc.date.issued	2017
dc.identifier.citation	Cells, Tissues, Organs: in vivo, in vitro, 2017, 204, (3-4), pp. 191-198
dc.identifier.issn	1422-6405
dc.identifier.issn	1422-6421
dc.identifier.uri	http://hdl.handle.net/10453/160846
dc.description.abstract	Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures. To evaluate the validity of VCSs in recapitulating pathophysiological processes typical of the in vivo heart, such as cardiac fibrosis, we then treated VCSs with transforming growth factor beta 1 (TGFβ1), a known profibrotic agent. Our mRNA analysis demonstrated that TGFβ1-treated VCSs present elevated levels of expression of connective tissue growth factor, fibronectin, and TGFβ1 when compared to control cultures. We demonstrated a dramatic increase in collagen deposition following TGFβ1 treatment in VCSs in the PicroSirius Red-stained sections. Doxorubicin, a renowned cardiotoxic and profibrotic agent, triggered apoptosis and disrupted vascular networks in VCSs. Taken together, our findings demonstrate that VCSs are a valid model for the study of the mechanisms involved in cardiac fibrosis, with the potential to be used to investigate novel mechanisms and therapeutics for treating and preventing cardiac fibrosis in vitro.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Karger Publishers
dc.relation.ispartof	Cells, Tissues, Organs: in vivo, in vitro
dc.relation.isbasedon	10.1159/000477436
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.subject.classification	Developmental Biology
dc.subject.mesh	Animals
dc.subject.mesh	Apoptosis
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Extracellular Matrix
dc.subject.mesh	Fibrosis
dc.subject.mesh	Humans
dc.subject.mesh	Imaging, Three-Dimensional
dc.subject.mesh	Mice
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Animals
dc.subject.mesh	Apoptosis
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Extracellular Matrix
dc.subject.mesh	Fibrosis
dc.subject.mesh	Humans
dc.subject.mesh	Imaging, Three-Dimensional
dc.subject.mesh	Mice
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Extracellular Matrix
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Fibrosis
dc.subject.mesh	Imaging, Three-Dimensional
dc.subject.mesh	Apoptosis
dc.title	Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis.
dc.type	Journal Article
utslib.citation.volume	204
utslib.location.activity	Switzerland
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
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	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-08-25T06:28:06Z
pubs.issue	3-4
pubs.publication-status	Published
pubs.volume	204
utslib.citation.issue	3-4

Abstract:

Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures. To evaluate the validity of VCSs in recapitulating pathophysiological processes typical of the in vivo heart, such as cardiac fibrosis, we then treated VCSs with transforming growth factor beta 1 (TGFβ1), a known profibrotic agent. Our mRNA analysis demonstrated that TGFβ1-treated VCSs present elevated levels of expression of connective tissue growth factor, fibronectin, and TGFβ1 when compared to control cultures. We demonstrated a dramatic increase in collagen deposition following TGFβ1 treatment in VCSs in the PicroSirius Red-stained sections. Doxorubicin, a renowned cardiotoxic and profibrotic agent, triggered apoptosis and disrupted vascular networks in VCSs. Taken together, our findings demonstrate that VCSs are a valid model for the study of the mechanisms involved in cardiac fibrosis, with the potential to be used to investigate novel mechanisms and therapeutics for treating and preventing cardiac fibrosis in vitro.

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http://hdl.handle.net/10453/160846