Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.
Bottom Line: Here we show that blood vessels direct the migrating cords of Schwann cells.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.
Affiliation: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.Show MeSH
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Mentions: Confocal microscopy analysis of the SCs entering into the bridge demonstrated a close association of the migrating SC cords and the polarized blood vessels (Figure 3A). Moreover, at later time points when the SCs had migrated further into the bridge, these interactions were maintained (Figure 3B). Analysis of matrix components of the bridge showed that fibronectin filled the space between the cells throughout the bridge and that strands of elastin also permeated the bridge region. In contrast, laminin and collagen I and IV could be detected only around the blood vessels (Figure S3A). To quantify the degree and specificity of the interactions between the SCs and the blood vessels, we measured the shortest distance between the nuclei of SCs at the leading edge and their closest blood vessel and compared it to the distance of other cell types present in the bridge. We found that the majority of SCs were extremely close (<10 μm) to blood vessels with the population showing a strong distribution toward the blood vessels, whereas the other cell types had a more random distribution within the bridge (Figure 3C). Moreover, the degree of interaction between SCs and blood vessels was probably underestimated, as we frequently observed SCs interacting with blood vessels via long protrusions while the nuclei were further away.
Affiliation: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.