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: To test whether SCs could interact directly with blood vessels in a simplified system, we co-cultured GFP-positive rat SCs with human umbilical vein endothelial cells (HUVECs), which had been coated onto beads and then placed into a fibrin matrix to form capillary-like structures (Nakatsu et al., 2003). Time-lapse microscopy showed that the vast majority of SCs interacted with the endothelial cell tubules and migrated along them (Figures 4A and S4A; Movie S3). Importantly, confocal microscopy images confirmed that the migrating SCs made direct physical contacts with the ECs as observed in vivo (Figure S4B). A small proportion of the SCs remained within the matrix (<15%) (Figure S4A), yet while these cells were able to form protrusions they were unable to migrate efficiently (Movie S3). In contrast, and consistent with other studies (Hakkinen et al., 2011), we found that fibroblasts, when added to the matrix, did not interact specifically with the tubules but instead spread and migrated within the matrix (Figure S4C). We confirmed that SCs directly migrated along blood vessels by generating tubules of HUVECs in a second matrix, Matrigel and found that SCs migrated efficiently along them (Movie S3). This demonstrates that SCs, unlike fibroblasts, are unable to migrate efficiently within a 3D matrix unless they associate with a scaffold of EC tubules.
Affiliation: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK.