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dc.contributor.author
Fernandes, Andreia
dc.contributor.author
Miéville, Arnaud
dc.contributor.author
Grob, Franziska
dc.contributor.author
Yamashita, Tadahiro
dc.contributor.author
Mehl, Julia
dc.contributor.author
Hosseini, Vahid
dc.contributor.author
Emmert, Maximilian Y.
dc.contributor.author
Falk, Volkmar
dc.contributor.author
Vogel, Viola
dc.date.accessioned
2022-10-24T06:09:10Z
dc.date.available
2022-08-20T10:07:06Z
dc.date.available
2022-08-23T06:38:08Z
dc.date.available
2022-10-20T14:56:25Z
dc.date.available
2022-10-20T14:56:52Z
dc.date.available
2022-10-24T06:09:10Z
dc.date.issued
2022-10-05
dc.identifier.issn
2198-3844
dc.identifier.other
10.1002/advs.202202317
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/565124
dc.identifier.doi
10.3929/ethz-b-000565124
dc.description.abstract
Intimal hyperplasia (IH) represents a major challenge following cardiovascular interventions. While mechanisms are poorly understood, the inefficient preventive methods incentivize the search for novel therapies. A vessel-on-a-dish platform is presented, consisting of direct-contact cocultures with human primary endothelial cells (ECs) and smooth muscle cells (SMCs) exposed to both laminar pulsatile and disturbed flow on an orbital shaker. With contractile SMCs sitting below a confluent EC layer, a model that successfully replicates the architecture of a quiescent vessel wall is created. In the novel IH model, ECs are seeded on synthetic SMCs at low density, mimicking reendothelization after vascular injury. Over 3 days of coculture, ECs transition from a network conformation to confluent 2D islands, as promoted by pulsatile flow, resulting in a “defected” EC monolayer. In defected regions, SMCs incorporated plasma fibronectin into fibers, increased proliferation, and formed multilayers, similarly to IH in vivo. These phenomena are inhibited under confluent EC layers, supporting therapeutic approaches that focus on endothelial regeneration rather than inhibiting proliferation, as illustrated in a proof-of-concept experiment with Paclitaxel. Thus, this in vitro system offers a new tool to study EC-SMC communication in IH pathophysiology, while providing an easy-to-use translational disease model platform for low-cost and high-content therapeutic development.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley-VCH
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
drug screening
en_US
dc.subject
endothelial cell networks
en_US
dc.subject
flow
en_US
dc.subject
in vitro coculture model
en_US
dc.subject
vascular injury
en_US
dc.title
Endothelial-Smooth Muscle Cell Interactions in a Shear-Exposed Intimal Hyperplasia on-a-Dish Model to Evaluate Therapeutic Strategies
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2022-08-15
ethz.journal.title
Advanced Science
ethz.journal.volume
9
en_US
ethz.journal.issue
28
en_US
ethz.journal.abbreviated
Adv. Sci.
ethz.pages.start
2202317
en_US
ethz.size
18 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Weinheim
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03640 - Vogel, Viola / Vogel, Viola
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09667 - Falk, Volkmar / Falk, Volkmar
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03640 - Vogel, Viola / Vogel, Viola
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09667 - Falk, Volkmar / Falk, Volkmar
ethz.date.deposited
2022-08-20T10:07:12Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-10-20T14:56:53Z
ethz.rosetta.lastUpdated
2023-02-07T07:17:34Z
ethz.rosetta.versionExported
true
ethz.COinS
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