A Multilevel Screening Strategy Defines a Molecular Fingerprint of Proregenerative Olfactory Ensheathing Cells and Identifies SCARB2, a Protein That Improves Regenerative Sprouting of Injured Sensory Spinal Axons

The Journal of Neuroscience, 2013 · DOI: 10.1523/JNEUROSCI.1002-13.2013 · Published: July 3, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Olfactory ensheathing cells (OECs) have neuro-restorative properties in animal models for spinal cord injury, stroke, and amyotrophic lateral sclerosis. The study used a multistep screening approach to discover genes specifically contributing to the regeneration-promoting properties of OECs. SCARB2, a protein that promotes cholesterol secretion, was found to be a potent enhancer of regenerative sprouting and contributes to OEC-mediated neuronal repair.

Study Duration

67 days CTB tracer injection

Participants

Adult female Fischer (F344) rats (180–220 g, 8–10 weeks of age)

Evidence Level

Not specified

Key Findings

1
Sixteen genes in OECs (ADAMTS1, BM385941, FZD1, GFRA1, LEPRE1, NCAM1, NID2, NRP1, MSLN, RND1, S100A9, SCARB2, SERPINI1, SERPINF1, TGFB2, and VAV1) significantly reduced outgrowth of cocultured DRG neurons.
2
Six genes (CX3CL1, FZD1, LEPRE1, S100A9, SCARB2, and SERPINI1) enhanced and one (TIMP2) inhibited neurite growth.
3
SCARB2 significantly increased the number of regenerating DRG axons that grew toward the center of a spinal cord lesion in rats.

Research Summary

The study used a multistep screening approach to discover genes specifically contributing to the regeneration-promoting properties of OECs. Microarray screening and functional characterization identified 102 genes, with 16 genes significantly reducing outgrowth of cocultured DRG neurons upon siRNA-mediated knockdown. SCARB2 was identified as a potent enhancer of regenerative sprouting, contributing to OEC-mediated neurorepair, and its overexpression significantly increased regenerating DRG axons in spinal cord lesions in rats.

Practical Implications

Therapeutic Target Identification

SCARB2 and other identified genes offer potential therapeutic targets for promoting nerve regeneration in spinal cord injuries.

OEC-Based Therapies

Understanding the molecular mechanisms of OECs can improve the development of OEC-based therapies for CNS repair.

Cholesterol Metabolism and Regeneration

The role of cholesterol metabolism in nerve regeneration, highlighted by SCARB2, warrants further investigation for therapeutic strategies.

Study Limitations

1
The study primarily used animal models (rats), and results may not directly translate to human physiology.
2
The focus was on a specific type of injury (dorsal column lesion), and findings might not generalize to other injury types or CNS regions.
3
The in vivo experiments involved ex vivo gene delivery of SCARB2, which may not fully replicate the natural expression patterns and interactions of SCARB2 in OECs.

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