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dc.contributor.author
Canepa, Daisy D.
dc.contributor.author
Casanova, Elisa A.
dc.contributor.author
Arvaniti, Eirini
dc.contributor.author
Tosevski, Vinko
dc.contributor.author
Märsmann, Sonja
dc.contributor.author
Eggerschwiler, Benjamin
dc.contributor.author
Halvachizadeh, Sascha
dc.contributor.author
Buschmann, Johanna
dc.contributor.author
Barth, André A.
dc.contributor.author
Plock, Jan A.
dc.contributor.author
Claassen, Manfred
dc.contributor.author
Pape, Hans-Christoph
dc.contributor.author
Cinelli, Paolo
dc.date.accessioned
2021-01-11T12:39:39Z
dc.date.available
2021-01-11T03:53:52Z
dc.date.available
2021-01-11T12:39:39Z
dc.date.issued
2021-01-06
dc.identifier.other
10.1186/s13287-020-02044-4
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/460925
dc.identifier.doi
10.3929/ethz-b-000460925
dc.description.abstract
Background The impressive progress in the field of stem cell research in the past decades has provided the ground for the development of cell-based therapy. Mesenchymal stromal cells obtained from adipose tissue (AD-MSCs) represent a viable source for the development of cell-based therapies. However, the heterogeneity and variable differentiation ability of AD-MSCs depend on the cellular composition and represent a strong limitation for their use in therapeutic applications. In order to fully understand the cellular composition of MSC preparations, it would be essential to analyze AD-MSCs at single-cell level. Method Recent advances in single-cell technologies have opened the way for high-dimensional, high-throughput, and high-resolution measurements of biological systems. We made use of the cytometry by time-of-flight (CyTOF) technology to explore the cellular composition of 17 human AD-MSCs, interrogating 31 markers at single-cell level. Subcellular composition of the AD-MSCs was investigated in their naïve state as well as during osteogenic commitment, via unsupervised dimensionality reduction as well as supervised representation learning approaches. Result This study showed a high heterogeneity and variability in the subcellular composition of AD-MSCs upon isolation and prolonged culture. Algorithm-guided identification of emerging subpopulations during osteogenic differentiation of AD-MSCs allowed the identification of an ALP+/CD73+ subpopulation of cells with enhanced osteogenic differentiation potential. We could demonstrate in vitro that the sorted ALP+/CD73+ subpopulation exhibited enhanced osteogenic potential and is moreover fundamental for osteogenic lineage commitment. We finally showed that this subpopulation was present in freshly isolated human adipose-derived stromal vascular fractions (SVFs) and that could ultimately be used for cell therapies. Conclusion The data obtained reveal, at single-cell level, the heterogeneity of AD-MSCs from several donors and highlight how cellular composition impacts the osteogenic differentiation capacity. The marker combination (ALP/CD73) can not only be used to assess the differentiation potential of undifferentiated AD-MSC preparations, but also could be employed to prospectively enrich AD-MSCs from the stromal vascular fraction of human adipose tissue for therapeutic applications.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central Ltd
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Identification of ALP+/CD73+ defining markers for enhanced osteogenic potential in human adipose-derived mesenchymal stromal cells by mass cytometry
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Stem Cell Research and Therapy
ethz.journal.volume
12
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
7
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03984 - Claassen, Manfred (ehemalig) / Claassen, Manfred (former)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03984 - Claassen, Manfred (ehemalig) / Claassen, Manfred (former)
ethz.date.deposited
2021-01-11T03:54:09Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-01-11T12:39:48Z
ethz.rosetta.lastUpdated
2021-02-15T23:06:35Z
ethz.rosetta.versionExported
true
ethz.COinS
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