TLR4-dependent shaping of the wound site by MSCs accelerates wound healing
| Autor: | Hartmut Geiger, Karin Scharffetter-Kochanek, Karmveer Singh, Saira Munir, Linda Krug, Gudrun Strauss, Dongsheng Jiang, Abhijit Basu, Pallab Maity, Meinhard Wlaschek, Philipp Haas |
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| Rok vydání: | 2019 |
| Předmět: |
adaptive transcriptomic response
Immunology Biology Regenerative Medicine Biochemistry MSC‐based therapy Article Transcriptome 03 medical and health sciences Mice 0302 clinical medicine neutrophils Sense (molecular biology) Genetics Animals Receptor Molecular Biology Tissue homeostasis 030304 developmental biology Skin LPS sensing 0303 health sciences Wound Healing mesenchymal stem cells Macrophages Mesenchymal stem cell Articles Adaptive Transcriptomic Response Lps Sensing Mesenchymal Stem Cells Msc-based Therapy Neutrophils Cell biology Toll-Like Receptor 4 TLR4 Wound healing Reprogramming 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | EMBO Reports EMBO Rep. 21:e48777 (2020) |
| ISSN: | 1469-3178 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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