Human Astrocytes Derived from Glial Restricted Progenitors Support Regeneration of the Injured Spinal Cord

JOURNAL OF NEUROTRAUMA, 2013 · DOI: 10.1089/neu.2013.2915 · Published: June 15, 2013

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This research investigates the potential of using human glial restricted progenitors (hGRP) and their derived astrocytes to promote spinal cord regeneration after injury. The study compares different methods of differentiating hGRP into astrocytes and tests their effects on axon regeneration in a rat model of spinal cord injury. The study found that both hGRP and their derived astrocytes survived transplantation into the injured spinal cord and promoted the regeneration of host sensory axons into the graft site. Notably, there were no significant differences in regenerative outcomes among the different groups of cells tested. The results suggest that pre-differentiating hGRP may not be necessary for therapeutic efficacy, and that using readily available hGRP from frozen stocks could be a viable option for transplantation, potentially simplifying the process for clinical applications.

Study Duration

5 weeks post-transplant

Participants

Adult female athymic rats and Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
hGRP and hGRP-derived astrocytes showed excellent survival and expressed astrocyte markers after transplantation into a spinal cord lesion.
2
Both hGRP and hGRP-derived astrocytes supported axonal growth and regeneration into the graft/lesion site.
3
hGRP taken directly from frozen stocks behaved similarly to differentiated hGRP and also supported regeneration of host axons into the lesion.

Research Summary

This study meticulously characterized the phenotypic diversity and plasticity of hGRP prepared by a Good Manufacturing Practice (GMP) production standard for possible clinical application. The study found that hGRP and hGRP-derived astrocytes survived transplantation into the injured spinal cord, expressed astrocyte markers, and supported axonal growth and regeneration into the graft/lesion site. The research suggests that a lengthy process of pre-differentiation may not be necessary for therapeutic application and that hGRP taken directly from frozen stocks can be used.

Practical Implications

Clinical Translation

The use of readily available, banked hGRP simplifies the process for potential clinical applications in spinal cord injury treatment.

Therapeutic Strategies

The permissive nature of embryonic astrocytes may require combination with other therapeutic interventions for functional recovery through long-distance axonal regeneration.

GMP-produced hGRP as a Tool

hGRP prepared by a GMP production standard are a powerful in vivo tool that can be readily expanded and banked for research.

Study Limitations

1
Axonal regeneration was observed into, but not out of, the graft site.
2
Assessment of behavioral recovery was not included in this study.
3
The study did not investigate long-term effects beyond five weeks post-transplantation.

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