Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates

World Journal of Stem Cells, 2021 · DOI: 10.4252/wjsc.v13.i5.452 · Published: May 26, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This research explores a novel approach to treating spinal cord injury (SCI) by transplanting directly reprogrammed neural precursor cells (drNPCs) into non-human primates. The study found that this transplantation was safe and led to improvement in spinal cord function after acute SCI. The functional improvement was associated with directed drNPCs migration to the areas of active growth cone formation which may provide exosome and paracrine trophic support, thereby further supporting the regeneration processes.

Study Duration

12 wk

Participants

Seven mature Macaca mulatta male NHPs

Evidence Level

Not specified

Key Findings

1
Animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somato-sensory evoked potential and motor evoked potential of injured pathways.
2
drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk, migrating to areas of axon growth cones.
3
The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.

Research Summary

The study investigates the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells (drNPCs) in non-human primates with spinal cord injury (SCI). The results showed that animals receiving drNPC transplants demonstrated significant recovery of paralyzed hindlimbs and improved neurophysiological responses. Immunohistochemical analysis revealed that drNPCs maintained multipotency and migrated to areas of axon growth, suggesting a role in supporting regeneration processes.

Practical Implications

Regenerative Therapy

drNPC transplantation presents a potential regenerative therapy for spinal cord injury.

Clinical Translation

The study highlights the importance of using non-human primate models for preclinical testing to improve the translational relevance to human SCI.

Therapeutic Mechanism

The findings suggest that drNPCs may promote functional recovery through paracrine support and activation of regeneration processes, rather than direct neuronal differentiation.

Study Limitations

1
The study used allogeneic rather than autologous drNPC cells, which may have impacted the survival rate of transplanted cells.
2
The absence of immunosuppressive therapy may have contributed to the low survival rate of the graft.
3
Unravelling the mechanism of drNPC based efficacy was beyond the scope of the study

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