Origins of Neural Progenitor Cell-Derived Axons Projecting Caudally after Spinal Cord Injury

Abstract

Summary: Neural progenitor cells (NPCs) transplanted into sites of spinal cord injury (SCI) extend large numbers of axons into the caudal host spinal cord. We determined the precise locations of neurons in the graft that extend axons into the caudal host spinal cord using AAV9-Cre-initiated retrograde tracing into floxed-TdTomato-expressing NPC grafts. 7,640 ± 630 grafted neurons extended axons to a single caudal host spinal cord site located 2 mm beyond the lesion, 5 weeks post injury. While caudally projecting axons arose from neurons located in all regions of the graft, the majority of caudally projecting graft neurons (53%) were located within the caudal one-third of the graft. Numerous host corticospinal axons formed monosynaptic projections onto caudally projecting graft neurons; however, we find that the majority of host axonal neuronal projections formed by neural progenitor cell interneuronal “relays” across sites of SCI are likely polysynaptic in nature. : In this article, Tuszynski and colleagues show that grafted neurons derived from neural progenitor cells in the sites of spinal cord injury extend a large number of axons into the caudal host spinal cord. The majority of caudally projecting neurons (53%) were located within the caudal portion of the graft. Numerous host corticospinal axons formed monosynaptic projections onto caudally projecting graft neurons. Keywords: spinal cord injury, neural stem cells, neural progenitor cells, axonal growth, axonal regeneration