Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785648 | ||
| 005 | 20190713030954.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2016 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000114095 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms11051 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/114095 | ||
| 245 | 0 | 0 | |a Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration |h [Elektronische Daten] |c [Mikaël M. Martino, Kenta Maruyama, Gisela A. Kuhn, Takashi Satoh, Osamu Takeuchi, Ralph; id_orcid 0000-0002-5811-7725 Müller, Shizuo Akira] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Martino |D Mikaël M. |e joint author | |
| 700 | 1 | |a Maruyama |D Kenta |e joint author | |
| 700 | 1 | |a Kuhn |D Gisela A. |e joint author | |
| 700 | 1 | |a Satoh |D Takashi |e joint author | |
| 700 | 1 | |a Takeuchi |D Osamu |e joint author | |
| 700 | 1 | |a Müller |D Ralph; id_orcid 0000-0002-5811-7725 |e joint author | |
| 700 | 1 | |a Akira |D Shizuo |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 7, p. 11051 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/114095 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/114095 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Martino |D Mikaël M. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Maruyama |D Kenta |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Kuhn |D Gisela A. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Satoh |D Takashi |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Takeuchi |D Osamu |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Müller |D Ralph; id_orcid 0000-0002-5811-7725 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Akira |D Shizuo |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 7, p. 11051 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||