Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis.
- 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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ContentServer.pdf | 339.59 kB | Adobe PDF |
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Full metadata record
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 |
|
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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