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TLR4-dependent shaping of the wound site by MSCs accelerates wound healing.
EMBO Rep. 21:e48777 (2020)
We here address the question whether the unique capacity of mesenchymal stem cells to re-establish tissue homeostasis depends on their potential to sense pathogen-associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS-treated MSCs as deduced from RNAseq analysis and its validation. A network of genes mediating the adaptive response through the Toll-like receptor 4 (TLR4) pathway responsible for neutrophil and macrophage recruitment and their activation profoundly contributes to enhanced wound healing. In fact, injection of LPS-primed MSCs silenced for TLR4 fails to accelerate wound healing. These unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds.
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7.497
1.452
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adaptive Transcriptomic Response ; Lps Sensing ; Mesenchymal Stem Cells ; Msc-based Therapy ; Neutrophils ; Wound Healing
Language
english
Publication Year
2020
HGF-reported in Year
2020
ISSN (print) / ISBN
1469-221X
e-ISSN
1469-3178
Journal
EMBO Reports
Quellenangaben
Volume: 21,
Issue: 5,
Article Number: e48777
Publisher
EMBO Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s)
30202 - Environmental Health
Research field(s)
Lung Research
PSP Element(s)
G-554000-001
Scopus ID
85081721742
PubMed ID
32162777
WOS ID
WOS:000532232800025
Erfassungsdatum
2020-05-19