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

Stem Cell Reports, 2019 · DOI: https://doi.org/10.1016/j.stemcr.2019.05.011 · Published: July 9, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how neural progenitor cells (NPCs) can help restore connections in the spinal cord after injury. When NPCs are transplanted into the injured spinal cord, they send out axons, which are like wires, down the spinal cord. The researchers wanted to find out where in the transplanted cells these axons originate. They discovered that most of these axons come from the cells located in the tail end of the transplant. The study also looked at how these transplanted cells connect with the existing spinal cord. They found that while some direct connections are formed, most connections are more complex, involving multiple steps.

Study Duration

5 weeks

Participants

7 mice, 6 rats

Evidence Level

Not specified

Key Findings

1
The majority (53%) of caudally projecting graft neurons were located within the caudal one-third of the graft.
2
Host corticospinal axons can form monosynaptic connections with caudally projecting graft neurons, but these are relatively rare (3.9% ± 0.9% of TdTomato-expressing neurons).
3
Most projections across a graft placed in a site of SCI are likely to be polysynaptic.

Research Summary

Neural progenitor cells (NPCs) transplanted into sites of spinal cord injury (SCI) extend large numbers of axons into the caudal host spinal cord. 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.

Practical Implications

Optimizing Graft Placement

Placing the caudal end of the NPC graft in close proximity to the caudal host spinal cord may enhance axonal outgrowth into the host tissue.

Enhancing Monosynaptic Connections

Strategies to increase the proportion of monosynaptic connections from host to graft to host could potentially improve functional recovery after SCI.

Targeting Host Axon Regeneration

Increasing the distance of host axon regeneration into grafts, perhaps by targeting mTOR pathways, may promote more monosynaptic connections to grafted neurons.

Study Limitations

1
Contacts were only quantified onto graft neuronal somata and not dendrites, potentially underestimating the number of monosynaptic connections.
2
The study could not be performed in a blinded manner.
3
Cre-dependent rat donor cell grafts are not available.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury