Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Diego Reginensi, Patricia Carulla, Sara Nocentini, Oscar Seira, Xavier Serra-Picamal, Abel Torres-Espín, Andreu Matamoros-Angles, Rosalina Gavín, María Teresa Moreno-Flores, Francisco Wandosell, Josep Samitier, Xavier Trepat, Xavier Navarro, José Antonio Del Río

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

© 2015 Springer Basel. Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.
Original languageEnglish
Pages (from-to)2719-2737
JournalCellular and Molecular Life Sciences
Volume72
Issue number14
DOIs
Publication statusPublished - 24 Jul 2015

Keywords

  • Cell migration
  • Chondroitin sulphate proteoglycans
  • Nogo receptor ectodomain
  • Olfactory ensheathing cells
  • Traction force microscopy

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