Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury

JCI Insight, 2022 · DOI: https://doi.org/10.1172/jci.insight.158000 · Published: August 22, 2022

Spinal Cord Injury Rehabilitation Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates whether combining neural progenitor cell (NPC) grafts with rehabilitation can improve functional recovery after chronic spinal cord injury (SCI). Rats with severe spinal cord injuries received either rehabilitation, NPC grafts, both, or neither, one month after injury. The research found that only the combination of rehabilitation and grafting led to significant improvements in functional recovery. This suggests that both treatments are needed to promote neural plasticity and support recovery after chronic and severe SCI. The improved functional outcomes were linked to an increase in the regeneration of host corticospinal axons into the grafts, driven by rehabilitation. This highlights the synergistic effect of rehabilitation and stem cell therapy in promoting recovery after chronic SCI.

Study Duration

12 weeks post-treatment

Participants

150 adult female Fischer 344 rats

Evidence Level

Not specified

Key Findings

1
The combination of rehabilitation and NPC grafting significantly improved functional recovery in rats with chronic SCI, whereas either treatment alone was not effective.
2
Rehabilitation enhanced the regeneration of injured host corticospinal axons into the NPC grafts in the lesion site.
3
Transplanted NPCs differentiated into neurons and glia, and extended large numbers of axons into the host spinal cord.

Research Summary

The study examines whether neural progenitor cell (NPC) grafts after chronic delays also support recovery and whether intensive rehabilitation further enhances recovery after severe bilateral cervical contusion in rats. The key finding is that only the combination of rehabilitation and grafting significantly improved functional recovery, indicating a synergistic effect. Improved functional outcomes were associated with a rehabilitation-induced increase in host corticospinal axon regeneration into grafts, highlighting the importance of rehabilitation in driving neural plasticity.

Practical Implications

Clinical Translation

The findings suggest that incorporating routine, intensive, and coordinated rehabilitation strategies into the clinical design of candidate therapies for CNS disorders that advance to human trials is crucial.

Therapeutic Strategies

The study highlights the potential of combining proregenerative therapies (like NPC grafts) with rehabilitation to achieve greater anatomical and functional recovery after SCI.

Rehabilitation Timing

The research challenges the dogma that rehabilitation is only effective in the subacute phase of injury, suggesting it can also provide benefits in chronic SCI when combined with other therapies.

Study Limitations

1
The functional outcomes of the NPC transplant and rehabilitation and rehabilitation-alone groups did not differ statistically from each other, even though only the NPC transplant and rehabilitation group reached statistical significance in differing from lesioned controls.
2
The study used a rat model, and the results may not be directly translatable to human SCI due to differences in physiology and injury characteristics.
3
The study did not detect sprouting of corticospinal projections to the spinal cord rostral to the lesion, and future studies will accordingly focus on sprouting in other locations.

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