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dc.contributor.author
Emmert, Maximilian Y.
dc.contributor.author
Weber, Benedikt
dc.contributor.author
Wolint, Petra
dc.contributor.author
Frauenfelder, Thomas
dc.contributor.author
Zeisberger, Steffen M.
dc.contributor.author
Behr, Luc
dc.contributor.author
Sammut, Sebastien
dc.contributor.author
Scherman, Jacques
dc.contributor.author
Brokopp, Chad E.
dc.contributor.author
Schwartländer, Ruth
dc.contributor.author
Vogel, Viola
dc.contributor.author
Vogt, Peter
dc.contributor.author
Grünenfelder, Jürg
dc.contributor.author
Alkadhi, Hatem
dc.contributor.author
Falk, Volkmar
dc.contributor.author
Boss, Andreas
dc.contributor.author
Hoerstrup, Simon P.
dc.date.accessioned
2018-07-26T09:13:06Z
dc.date.available
2017-06-10T15:21:56Z
dc.date.available
2018-07-26T09:13:06Z
dc.date.issued
2013-03-22
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0057759
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/65117
dc.identifier.doi
10.3929/ethz-b-000065117
dc.description.abstract
Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
8
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e57759
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA
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.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
ethz.date.deposited
2017-06-10T15:24:34Z
ethz.source
ECIT
ethz.identifier.importid
imp59365075d023164550
ethz.ecitpid
pub:103682
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-19T11:01:47Z
ethz.rosetta.lastUpdated
2018-11-07T17:24:21Z
ethz.rosetta.versionExported
true
ethz.COinS
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