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The Journal of Neuroscience, May 17, 2006, 26(20):5347-5359; doi:10.1523/JNEUROSCI.1111-06.2006

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

Erika Pastrana, Maria Teresa Moreno-Flores, Esteban N. Gurzov, Jesus Avila, Francisco Wandosell, and Javier Diaz-Nido

Centro de Biologia Molecular "Severo Ochoa," Universidad Autonoma de Madrid, 28049 Madrid, Spain

Correspondence should be addressed to Javier Diaz-Nido, Centro de Biologia Molecular "Severo Ochoa," Universidad Autonoma de Madrid, 28049 Madrid, Spain. Email: javier.diaznido{at}uam.es

The molecular mechanisms used by olfactory ensheathing cells (OECs) to promote repair in the damaged adult mammalian CNS remain unknown. Thus, we used microarrays to analyze three OEC populations with different capacities to promote axonal regeneration in cultured rat retinal neurons. Gene expression in "long-term cultured OECs" that do not stimulate adult axonal outgrowth was compared with that of "primary olfactory ensheathing cells" and the immortalized OEC cell line TEG3. In this way, we identified a number of candidate genes that might play a role in promoting adult axonal regeneration. Among these genes, it was striking that both the matrix metalloproteinase 2 (MMP2) and an inhibitor of this protease were represented. The disruption of MMP2 activity in TEG3 cells impaired their capacity to trigger axon regeneration in cultured adult retinal neurons. Furthermore, the MMP2 protein was detected in grafts of OECs that elicited robust axonal regeneration in the injured spinal cord of adult rats in vivo. These data suggest that MMP2 does indeed participate in adult axonal regeneration induced by OECs.

Key words: axon regeneration; matrix metalloproteinase; microarray; olfactory ensheathing cell; retinal ganglion cell; spinal cord injury

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Received Feb. 14, 2006; accepted April 3, 2006.

Correspondence should be addressed to Javier Diaz-Nido, Centro de Biologia Molecular "Severo Ochoa," Universidad Autonoma de Madrid, 28049 Madrid, Spain. Email: javier.diaznido{at}uam.es

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