<div class="csl-bib-body">
<div class="csl-entry">Thomas, D., Marsico, G., Isa, L. M. I., Thirumaran, A., Chen, X., Lukasz, B., Fontana, G., Rodriguez, B., Marchetti-Deschmann, M., OBrien, T., & Pandit, A. (2020). Temporal Changes Guided by Mesenchymal Stem Cells on a 3D Microgel Platform Enhances Angiogenesis In Vivo at a Low-Cell Dose. <i>Proceedings of the National Academy of Sciences</i>, <i>117</i>(32), 19033–19044. https://doi.org/10.1073/pnas.2008245117</div>
</div>
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dc.identifier.issn
0027-8424
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/140538
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dc.description.abstract
Therapeutic factors secreted by mesenchymal stem cells (MSCs) promote angiogenesis in vivo. However, delivery of MSCs in the absence of a cytoprotective environment offers limited efficacy due to low cell retention, poor graft survival, and the nonmaintenance of a physiologically relevant dose of growth factors at the injury site. The delivery of stem cells on an extracellular matrix (ECM)- based platform alters cell behavior, including migration, prolifera- tion, and paracrine activity, which are essential for angiogenesis. We demonstrate the biophysical and biochemical effects of precon- ditioning human MSCs (hMSCs) for 96 h on a three-dimensional (3D) ECM-based microgel platform. By altering the macromolecular con- centration surrounding cells in the microgels, the proangiogenic phenotype of hMSCs can be tuned in a controlled manner through cell-driven changes in extracellular stiffness and "outside-in" integ- rin signaling. The softest microgels were tested at a low cell dose (5 × 104 cells) in a preclinical hindlimb ischemia model showing accelerated formation of new blood vessels with a reduced inflam- matory response impeding progression of tissue damage. Molecular analysis revealed that several key mediators of angiogenesis were up-regulated in the low-cell-dose microgel group, providing a mech- anistic insight of pathways modulated in vivo. Our research adds to current knowledge in cell-encapsulation strategies by highlighting the importance of preconditioning or priming the capacity of bio- materials through cell-material interactions. Obtaining therapeutic efficacy at a low cell dose in the microgel platform is a promising clinical route that would aid faster tissue repair and reperfusion in "no-option" patients suffering from peripheral arterial diseases, such as critical limb ischemia (CLI).
en
dc.language.iso
en
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dc.relation.ispartof
Proceedings of the National Academy of Sciences
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dc.title
Temporal Changes Guided by Mesenchymal Stem Cells on a 3D Microgel Platform Enhances Angiogenesis In Vivo at a Low-Cell Dose
en
dc.type
Artikel
de
dc.type
Article
en
dc.description.startpage
19033
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dc.description.endpage
19044
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dc.type.category
Original Research Article
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tuw.container.volume
117
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tuw.container.issue
32
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tuw.journal.peerreviewed
true
-
tuw.peerreviewed
true
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wb.publication.intCoWork
International Co-publication
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tuw.researchTopic.id
M6
-
tuw.researchTopic.id
M2
-
tuw.researchTopic.name
Biological and Bioactive Materials
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tuw.researchTopic.name
Materials Characterization
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tuw.researchTopic.value
50
-
tuw.researchTopic.value
50
-
dcterms.isPartOf.title
Proceedings of the National Academy of Sciences
-
tuw.publication.orgunit
E164-01-1 - Forschungsgruppe Massenspektrometrische Bio- und Polymeranalytik
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tuw.publisher.doi
10.1073/pnas.2008245117
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dc.identifier.eissn
1091-6490
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dc.description.numberOfPages
12
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tuw.author.orcid
0000-0001-7427-5523
-
tuw.author.orcid
0000-0002-6292-4933
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wb.sci
true
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wb.sciencebranch
Chemie
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wb.sciencebranch.oefos
1040
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wb.facultyfocus
Bioscience Technology
de
wb.facultyfocus
Bioscience Technology
en
wb.facultyfocus.faculty
E150
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item.openairetype
Artikel
-
item.openairetype
Article
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item.openairecristype
http://purl.org/coar/resource_type/c_18cf
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item.openairecristype
http://purl.org/coar/resource_type/c_18cf
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item.languageiso639-1
en
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item.cerifentitytype
Publications
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item.cerifentitytype
Publications
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item.fulltext
no Fulltext
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item.grantfulltext
restricted
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crisitem.author.dept
E164-01-1 - Forschungsgruppe Massenspektrometrische Bio- und Polymeranalytik
-
crisitem.author.orcid
0000-0002-8060-7851
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crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie