Premium
TLR4‐dependent shaping of the wound site by MSCs accelerates wound healing
Author(s) -
Munir Saira,
Basu Abhijit,
Maity Pallab,
Krug Linda,
Haas Philipp,
Jiang Dongsheng,
Strauss Gudrun,
Wlaschek Meinhard,
Geiger Hartmut,
Singh Karmveer,
ScharffetterKochanek Karin
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948777
Subject(s) - wound healing , mesenchymal stem cell , reprogramming , microbiology and biotechnology , biology , tlr4 , transcriptome , immunology , signal transduction , gene , gene expression , genetics
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 MSC s primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non‐primed MSC s. This correlates with a fundamental reprogramming of the transcriptome in LPS ‐treated MSC s as deduced from RNA seq analysis and its validation. A network of genes mediating the adaptive response through the Toll‐like receptor 4 ( TLR 4) pathway responsible for neutrophil and macrophage recruitment and their activation profoundly contributes to enhanced wound healing. In fact, injection of LPS ‐primed MSC s silenced for TLR 4 fails to accelerate wound healing. These unprecedented findings hold substantial promise to refine current MSC ‐based therapies for difficult‐to‐treat wounds.