Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.
Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.
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DOI：
10.1016/j.cell.2015.07.021
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发表时间：
2015-08-27
期刊：
影响因子：
64.5
通讯作者：
Lloyd AC
中科院分区：
文献类型：
--
作者：
Cattin AL;Burden JJ;Van Emmenis L;Mackenzie FE;Hoving JJ;Garcia Calavia N;Guo Y;McLaughlin M;Rosenberg LH;Quereda V;Jamecna D;Napoli I;Parrinello S;Enver T;Ruhrberg C;Lloyd AC
周围神经系统具有显著的再生能力，它可以修复完全切断的神经。这需要雪旺细胞集体迁移，引导再生的轴突通过新组织的“桥”，新组织的形成是为了重新连接被切断的神经。这里我们显示血管引导雪旺细胞的迁移索。这个多细胞过程是由缺氧引发的，被桥内的巨噬细胞选择性地感知，通过VEGF-A分泌诱导极化血管，缓解缺氧。然后，雪旺细胞利用血管作为“轨道”，带着再生的轴突穿过桥。重要的是，破坏体内新形成血管的组织，无论是通过抑制血管生成信号还是通过重新定向，都会损害雪旺细胞的方向性，导致神经修复缺陷。这项研究提供了重要的见解，如何多种细胞类型的编排是成人组织的再生所必需的。神经桥内缺氧被巨噬细胞选择性感知巨噬细胞衍生的VEGF-A诱导桥内极化血管血管被用作引导雪旺细胞在伤口上迁移的轨道巨噬细胞诱导的血管对神经再生至关重要修复受损的神经需要雪旺细胞在缺氧桥内巨噬细胞诱导的极化血管的引导下集体迁移。
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. Hypoxia within the nerve bridge is selectively sensed by macrophages Macrophage-derived VEGF-A induces a polarized vasculature within the bridge Blood vessels are used as tracks to direct Schwann cell migration across the wound Macrophage-induced blood vessels are essential for nerve regeneration Repairing a cut nerve requires collective migration of Schwann cells guided by a polarized vasculature that is induced by macrophages within the hypoxic bridge.