Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)–derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC–derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell–derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal–regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.

脊髓损伤（SCI）后的轴突再生会被髓磷脂相关的生长抑制分子减弱。我们报告说，大鼠髓磷脂刺激了移植到成年大鼠脊髓损伤部位的大鼠神经祖细胞 (NPC) 中出现的轴突的生长。当铺在髓磷脂基质上时，大鼠 NPC 和人诱导多能干细胞 (iPSC) 衍生的神经干细胞 (NSC) 的神经突生长增强了三倍。在体内，大鼠 NPC 和人类 iPSC 衍生的 NSC 通过成年中枢神经系统白质比通过灰质延伸更多数量的轴突，并且优先与大鼠宿主髓磷脂相关。机制研究排除了 Nogo 受体信号传导作为干细胞衍生轴突生长响应髓磷脂的介质。啮齿动物 NPC 的转录组筛选发现细胞粘附分子神经元生长调节剂 1 (Negr1) 是允许的轴突-髓磷脂相互作用的一种介质。髓磷脂相关蛋白对啮齿动物 NPC 的刺激作用受到发育调节，并涉及细胞外信号调节激酶 (ERK) 的直接激活。髓磷脂对 NPC/NSC 轴突生长的刺激作用应进一步研究，并有可能用于 SCI 后的神经修复。