Genes Associated with Adult Axon Regeneration Promoted by Olfactory Ensheathing Cells: A New Role for Matrix Metalloproteinase 2

The Journal of Neuroscience, 2006 · DOI: 10.1523/JNEUROSCI.1111-06.2006 · Published: May 17, 2006

Regenerative Medicine Neurology Genetics

Simple Explanation

Olfactory ensheathing cells (OECs) are a type of glial cell that support the growth of olfactory receptor axons. Because of this growth-promoting characteristic, OECs are potential candidates for cell transplantation to treat spinal cord injuries. This study compares gene expression in three OEC populations with different capacities to promote axonal regeneration to identify molecules that OECs use to promote axon regeneration in the adult CNS. The study found that matrix metalloproteinase 2 (MMP2) participates in adult axonal regeneration induced by OECs. Disrupting MMP2 activity impairs the capacity of OECs to trigger axon regeneration.

Study Duration

10 weeks

Participants

Adult male Wistar rats (n = 12)

Evidence Level

In vitro and in vivo study

Key Findings

1
MMP2 and its inhibitor Timp2 are candidate molecules that may promote and inhibit axonal regeneration, respectively. MMP2 was found to be present in medium conditioned by primary and TEG3 OECs, whereas MMP2 was barely detected in OEC Lp conditioned medium.
2
Inhibition and silencing of MMP2 reduced the capacity of TEG3 OECs to promote axon regeneration in adult retinal neurons in vitro.
3
MMP2 degrades the CSPGs present in the perineuronal net of adult retinal neurons which stimulates axon outgrowth.

Research Summary

The study compares the gene expression profiles of three OEC populations that differ in their capacity to promote adult axonal regeneration in vitro to identify molecules that OECs use to promote axon regeneration in the adult CNS. MMP2 was identified as a key factor in OEC-mediated axonal regeneration. Blocking or reducing MMP2 levels in OECs decreased their ability to promote axon regeneration in retinal neurons. MMP2 degrades CSPGs, which are inhibitory molecules found in the extracellular matrix surrounding neurons. Degradation of these molecules promotes axon outgrowth.

Practical Implications

Therapeutic Potential

MMP2 could be a therapeutic target for promoting axonal regeneration in spinal cord injuries.

Understanding OEC Mechanisms

MMP2 is part of the machinery that stimulates axon regeneration in the adult CNS, and is secreted by OEC grafts which may boost axonal regeneration and repair.

Targeting CSPGs

MMP2 could be used to degrade the CSPGs present in scar tissue of spinal cord injuries.

Study Limitations

1
The study focuses on MMP2, but other molecules may also play a role in axonal regeneration.
2
The in vitro findings may not fully translate to in vivo conditions.
3
The study is limited to rat models of spinal cord injury.

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