Journal
EMBO REPORTS
Volume 21, Issue 5, Pages -Publisher
WILEY
DOI: 10.15252/embr.201948777
Keywords
adaptive transcriptomic response; LPS sensing; mesenchymal stem cells; MSC-based therapy; neutrophils; wound healing
Categories
Funding
- Cellular and Molecular Mechanisms in Aging (CEMMA) [GRK 1789]
- Forderlinie Perspektivforderung Zellulare Entscheidungs- und Signalwege bei der Alterung of the Ministerium fur Wissenschaft, Forschung und Kunst Baden-Wurttemberg, Germany
- Collaborative Research Center 1149 for trauma research at Ulm
- Deutscher Akademischer Austauschdienst (DAAD)
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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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