Research ArticleNeuroscience

Adult rat myelin enhances axonal outgrowth from neural stem cells

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Science Translational Medicine  23 May 2018:
Vol. 10, Issue 442, eaal2563
DOI: 10.1126/scitranslmed.aal2563

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Editor's Summary

Myelin has been suggested to block regeneration of adult axons after spinal cord injury in mammals. In a new study, Poplawski et al. report that the outgrowth of axons from transplants of rat neural stem cells into sites of spinal cord injury in rat recipients may be stimulated by myelin, allowing axons to extend through the site of spinal cord injury. This growth depended in part on a cell adhesion molecule found on the surface of rodent NPCs called neuronal growth regulator 1 (Negr1). The finding that myelin may be able to stimulate neural repair in rodents suggests that this versatile substance should be investigated further for its potential to improve neural stem cell therapy for spinal cord injury.

Abstract

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.

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