TLR4-dependent Shaping of the Wound Site by MSCs Accelerates Wound Healing

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2020 Mar 13

PMID 32162777

Citations 31

Authors

Saira Munir

Abhijit Basu

Pallab Maity

Linda Krug

Philipp Haas

Dongsheng Jiang

Gudrun Strauss

Meinhard Wlaschek

Hartmut Geiger

Karmveer Singh

Karin Scharffetter-Kochanek

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The toxic effects of neutrophil extracellular traps on mesenchymal stem cells.

Aghayan A, Mirazimi Y, Nasehi L, Atashi A Mol Biol Rep. 2024; 52(1):30.

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Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles.

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Lipopolysaccharide Derived from Directly Promotes the Migration of Human Keratinocytes.

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