Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts

Abstract

Summary: Axonal regeneration after spinal cord injury (SCI) can be enhanced by activation of the intrinsic neuronal growth state and, separately, by placement of growth-enabling neural progenitor cell (NPC) grafts into lesion sites. Indeed, NPC grafts support regeneration of all host axonal projections innervating the normal spinal cord. However, some host axons regenerate only short distances into grafts. We examined whether activation of the growth state of the host injured neuron would elicit greater regeneration into NPC grafts. Rats received NPC grafts into SCI lesions in combination with peripheral “conditioning” lesions. Six weeks later, conditioned host sensory axons exhibited a significant, 9.6-fold increase in regeneration into the lesion/graft site compared with unconditioned axons. Regeneration was further enhanced 1.6-fold by enriching NPC grafts with phenotypically appropriate sensory neuronal targets. Thus, activation of the intrinsic host neuronal growth state and manipulation of the graft environment enhance axonal regeneration after SCI. : Kumamaru and colleagues demonstrate that activation of intrinsic growth state robustly enhances host sensory axonal regeneration into neural stem cell grafts. Regeneration of lesioned host sensory axons was further enhanced by enriching neural stem cell grafts with phenotypically appropriate sensory neuron targets. Keywords: neural stem cells, spinal cord injury, sensory, regeneration, conditioning lesion, Tlx3, spinal dorsal gray