Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration

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Date
2016Type
- Journal Article
Citations
Cited 89 times in
Web of Science
Cited 95 times in
Scopus
ETH Bibliography
yes
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Abstract
Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications. Show more
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https://doi.org/10.3929/ethz-b-000114095Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03565 - Müller, Ralph / Müller, Ralph
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Show all metadata
Citations
Cited 89 times in
Web of Science
Cited 95 times in
Scopus
ETH Bibliography
yes
Altmetrics