| Autor: |
Munir, Saira, Basu, Abhijit, Maity, Pallab, Krug, Linda, Haas, Philipp, Jiang, Dongsheng, Strauss, Gudrun, Wlaschek, Meinhard, Geiger, Hartmut, Singh, Karmveer, Scharffetter‐Kochanek, Karin |
| Zdroj: |
EMBO Reports; 5/6/2020, Vol. 21 Issue 5, p1-18, 18p |
| Abstrakt: |
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. Synopsis: Mesenchymal stem cells sense and shape their neighbourhood, accelerating tissue repair when injected into wounds. Exposure to LPS results in a profound transcriptomic shift in MSCs towards a multifaceted anti‐microbial defence and rapid wound closure. MSCs exposed to LPS change their transcriptome and show enhanced wound healing potential.LPS sensing of MSCs requires TLR4.TLR4‐dependent signalling promotes NET formation and recruitment of neutrophils and macrophages to the wound.Engulfment of apoptotic neutrophils induces macrophages to release TGFβ‐1, enhancing wound contraction. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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