Biofabrication of advancedin vitro3D models to study ischaemic and doxorubicin-induced myocardial damage.

Sharma, P; Liu Chung Ming, C; Wang, X; Bienvenu, LA; Beck, D; Figtree, G; Boyle, A; Gentile, C

Biofabrication of advancedin vitro3D models to study ischaemic and doxorubicin-induced myocardial damage.

Sharma, P Liu Chung Ming, C Wang, X Bienvenu, LA Beck, D Figtree, G Boyle, A Gentile, C

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Publisher:: IOP Publishing Ltd
Publication Type:: Journal Article
Citation:: Biofabrication, 2022, 14, (2)
Issue Date:: 2022-01-24

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Field	Value	Language
dc.contributor.author	Sharma, P
dc.contributor.author	Liu Chung Ming, C
dc.contributor.author	Wang, X
dc.contributor.author	Bienvenu, LA
dc.contributor.author	Beck, D
dc.contributor.author	Figtree, G
dc.contributor.author	Boyle, A
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.date.accessioned	2023-03-20T21:17:50Z
dc.date.available	2022-01-04
dc.date.available	2023-03-20T21:17:50Z
dc.date.issued	2022-01-24
dc.identifier.citation	Biofabrication, 2022, 14, (2)
dc.identifier.issn	1758-5082
dc.identifier.issn	1758-5090
dc.identifier.uri	http://hdl.handle.net/10453/167790
dc.description.abstract	Current preclinicalin vitroandin vivomodels of cardiac injury typical of myocardial infarction (MI, or heart attack) and drug induced cardiotoxicity mimic only a few aspects of these complex scenarios. This leads to a poor translation of findings from the bench to the bedside. In this study, we biofabricated for the first time advancedin vitromodels of MI and doxorubicin (DOX) induced injury by exposing cardiac spheroids (CSs) to pathophysiological changes in oxygen (O2) levels or DOX treatment. Then, contractile function and cell death was analyzed in CSs in control verses I/R and DOX CSs. For a deeper dig into cell death analysis, 3D rendering analyses and mRNA level changes of cardiac damage-related genes were compared in control verses I/R and DOX CSs. Overall,in vitroCSs recapitulated major features typical of thein vivoMI and drug induced cardiac damages, such as adapting intracellular alterations to O2concentration changes and incubation with cardiotoxic drug, mimicking the contraction frequency and fractional shortening and changes in mRNA expression levels for genes regulating sarcomere structure, calcium transport, cell cycle, cardiac remodelling and signal transduction. Taken together, our study supports the use of I/R and DOX CSs as advancedin vitromodels to study MI and DOX-induced cardiac damge by recapitulating their complexin vivoscenario.
dc.format	Electronic
dc.language	eng
dc.publisher	IOP Publishing Ltd
dc.relation.ispartof	Biofabrication
dc.relation.isbasedon	10.1088/1758-5090/ac47d8
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0903 Biomedical Engineering, 1004 Medical Biotechnology, 1099 Other Technology
dc.subject.mesh	Cardiotoxicity
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Heart
dc.subject.mesh	Humans
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Myocardium
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Myocardium
dc.subject.mesh	Heart
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Humans
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Doxorubicin
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Cardiotoxicity
dc.subject.mesh	Cardiotoxicity
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Heart
dc.subject.mesh	Humans
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Myocardium
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	RNA, Messenger
dc.title	Biofabrication of advancedin vitro3D models to study ischaemic and doxorubicin-induced myocardial damage.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	England
utslib.for	0903 Biomedical Engineering
utslib.for	1004 Medical Biotechnology
utslib.for	1099 Other Technology
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/Strength - AAI - Advanced Analytics Institute Research Centre
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	*
dc.date.updated	2023-03-20T21:17:48Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	2

Abstract:

Current preclinicalin vitroandin vivomodels of cardiac injury typical of myocardial infarction (MI, or heart attack) and drug induced cardiotoxicity mimic only a few aspects of these complex scenarios. This leads to a poor translation of findings from the bench to the bedside. In this study, we biofabricated for the first time advancedin vitromodels of MI and doxorubicin (DOX) induced injury by exposing cardiac spheroids (CSs) to pathophysiological changes in oxygen (O2) levels or DOX treatment. Then, contractile function and cell death was analyzed in CSs in control verses I/R and DOX CSs. For a deeper dig into cell death analysis, 3D rendering analyses and mRNA level changes of cardiac damage-related genes were compared in control verses I/R and DOX CSs. Overall,in vitroCSs recapitulated major features typical of thein vivoMI and drug induced cardiac damages, such as adapting intracellular alterations to O2concentration changes and incubation with cardiotoxic drug, mimicking the contraction frequency and fractional shortening and changes in mRNA expression levels for genes regulating sarcomere structure, calcium transport, cell cycle, cardiac remodelling and signal transduction. Taken together, our study supports the use of I/R and DOX CSs as advancedin vitromodels to study MI and DOX-induced cardiac damge by recapitulating their complexin vivoscenario.

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http://hdl.handle.net/10453/167790