Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves
Author(s)
Type
Journal Article
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.
Date Issued
2015-08-13
Date Acceptance
2015-06-30
Citation
Cell, 2015, 162 (5), pp.1127-1139
ISSN
0092-8674
Publisher
Elsevier
Start Page
1127
End Page
1139
Journal / Book Title
Cell
Volume
162
Issue
5
Copyright Statement
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
ENDOTHELIAL-CELLS
IN-VIVO
MIGRATION
METASTASIS
TISSUE
VEGF
MICE
ANGIOGENESIS
FIBROBLASTS
HOMEOSTASIS
Animals
Axons
Blood Vessels
Cell Hypoxia
Endothelial Cells
Inflammation
Macrophages
Male
Mice
Neovascularization, Physiologic
Peripheral Nerves
Rats
Rats, Sprague-Dawley
Regeneration
Schwann Cells
Vascular Endothelial Growth Factor A
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published