# Axial Identity of Spinal Cord Neural Progenitor Cell Grafts Is Dispensable for Regeneration and Functional Recovery After Spinal Cord Injury

## TL;DR

This study shows that spinal cord neural progenitor cells retain their identity after transplantation but do not need to match the injury site to promote recovery.

## Contribution

The study reveals that axial identity of transplanted NPCs is not essential for regeneration or functional recovery after spinal cord injury.

## Key findings

- A-NPCs and P-NPCs showed no differences in axon outgrowth or host axon regeneration.
- Both graft types supported similar levels of functional recovery and synaptic integration.
- P-NPCs maintained higher HoxC10 expression and Chx10-high V2a neuron proportions.

## Abstract

Neural progenitor cell (NPC) transplantation is a promising strategy for spinal cord injury repair, as graft-derived neurons can integrate into host circuitry and promote functional recovery. While the brain-regional and dorsoventral identities of NPCs are known to influence graft composition and performance, the importance of axial (rostrocaudal) identity, specifically whether NPCs must be matched to the spinal level of injury, remains poorly understood. To address this, we compared outcomes following transplantation of NPCs isolated from the anterior embryonic spinal cord (A-NPCs) versus the posterior spinal cord (P-NPCs) in a mouse model of C5 cervical dorsal column injury. Following transplantation, NPCs retained their intrinsic molecular axial identities; P-NPC grafts maintained significantly higher expression of the lumbar-associated gene HoxC10 and possessed a higher proportion of Chx10-high V2a neurons compared to A-NPCs. Despite these maintained molecular differences, A-NPC and P-NPC grafts were indistinguishable in neuronal and glial density, axon outgrowth, and their ability to support host axon regeneration, including the corticospinal tract. Long-term behavioral testing and retrograde transsynaptic tracing revealed no significant differences between groups in the recovery of skilled pellet reaching, grip strength, or synaptic integration with host cervical motor circuitry. These findings demonstrate that although transplanted NPCs retain their molecular axial identity in the adult injured environment, this identity is not a primary determinant of anatomical integration or functional outcome. Our findings suggest a degree of plasticity in graft-host interactions and indicate that strict segment-matching is not essential for the efficacy of NPC-based therapies in spinal cord injury.