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Cell. 2015 Aug 27;162(5):1127-39. doi: 10.1016/j.cell.2015.07.021. Epub 2015 Aug 13.

Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

Author information

1
MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.
2
Department of Cell Biology, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
3
UCL Cancer Institute, UCL, 72 Huntley Street, London WC1E 6DD, UK.
4
MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK; UCL Cancer Institute, UCL, 72 Huntley Street, London WC1E 6DD, UK. Electronic address: alison.lloyd@ucl.ac.uk.

Abstract

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

PMID:
26279190
PMCID:
PMC4553238
DOI:
10.1016/j.cell.2015.07.021
[Indexed for MEDLINE]
Free PMC Article

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