title: Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord.
abstract: 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.
authors.affiliation: Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Reginensi
authors.forename: Patricia
authors.initials: P
authors.lastname: Carulla
authors.forename: Sara
authors.initials: S
authors.lastname: Nocentini
authors.forename: Oscar
authors.initials: O
authors.lastname: Seira
authors.forename: Xavier
authors.initials: X
authors.lastname: Serra-Picamal
authors.forename: Abel
authors.initials: A
authors.lastname: Torres-Espín
authors.forename: Andreu
authors.initials: A
authors.lastname: Matamoros-Angles
authors.forename: Rosalina
authors.initials: R
authors.lastname: Gavín
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Moreno-Flores
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
authors.forename: Josep
authors.initials: J
authors.lastname: Samitier
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.forename: José Antonio
authors.initials: JA
authors.lastname: del Río
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology; D003001:Cloning, Molecular; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D046210:Microfluidic Analytical Techniques; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D000070816:Nogo Receptor 1; D009830:Olfactory Bulb / Q000166:cytology; D063345:Oligodendrocyte-Myelin Glycoprotein / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D013119:Spinal Cord Injuries / Q000628:therapy; D059008:Time-Lapse Imaging
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D063345:Oligodendrocyte-Myelin Glycoprotein; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat