Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury

PLoS ONE, 2010 · DOI: 10.1371/journal.pone.0015914 · Published: December 30, 2010

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This research explores a new approach to treating spinal cord injuries by transplanting human embryonic neural progenitors (hENPs) into damaged spinal cords of rats. Some hENPs were modified to produce a protein called Neurogenin-2 (Ngn2). The study found that transplanting hENPs that express Ngn2 improved motor function, while transplanting unmodified hENPs actually worsened the outcome. The improved motor function was linked to the restoration of serotonin fibers and appropriate location of serotonin receptors below the lesion site.

Study Duration

1 Month

Participants

36 female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Transplantation of hENPs expressing Ngn2 improved motor recovery after severe spinal cord compression in rats.
2
Transplantation of naïve hENPs was detrimental to functional recovery, worsening the outcome compared to injured-only animals.
3
Motor recovery was correlated with partial restoration of serotonin innervation and translocation of 5HT1A receptors.

Research Summary

The study investigated the effects of transplanting human embryonic neural progenitors (hENPs), with or without Neurogenin-2 (Ngn2) expression, into rats with severe spinal cord injuries. Results showed that Ngn2-expressing hENPs improved motor function and restored some serotonin-related nerve fiber and receptor patterns below the injury site. Importantly, transplanting unmodified hENPs worsened the outcome, highlighting potential risks of stem cell-based therapies for spinal cord injuries.

Practical Implications

Clinical Translation

The study's design, including delayed grafting and the use of human cells, aimed to mimic potential clinical applications for spinal cord injury treatment.

Therapeutic Target

Ngn2-expressing hENPs show promise as a therapeutic strategy for promoting functional recovery after spinal cord injury.

Safety Considerations

The detrimental effects of naïve hENP transplantation highlight the need for careful consideration and modification of cell-based therapies for spinal cord injury to avoid worsening outcomes.

Study Limitations

1
hENPs were not detectable 4 weeks after grafting.
2
The precise mechanisms underlying the positive outcomes observed with Ngn2-hENP transplantation require further investigation.
3
The study model involved severe compression of the dorsal aspect of the spinal cord, which might have initially produced major allodynia and/or hyperpathia phenomena.

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