caa a22 4500 60617642X CHVBK 20210128100747.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00018-015-1869-3 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1869-3 Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord [Elektronische Daten] [Diego Reginensi, Patricia Carulla, Sara Nocentini, Oscar Seira, Xavier Serra-Picamal, Abel Torres-Espín, Andreu Matamoros-Angles, Rosalina Gavín, María Moreno-Flores, Francisco Wandosell, Josep Samitier, Xavier Trepat, Xavier Navarro, José del Río] 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. Springer Basel, 2015 Olfactory ensheathing cells nationallicence Traction force microscopy nationallicence Chondroitin sulphate proteoglycans nationallicence Cell migration nationallicence Nogo receptor ectodomain nationallicence CGN : Cerebellar granule neurons nationallicence ChABC : Chondroitinase ABC nationallicence CNS : Central nervous system nationallicence CSPG : Chondroitin sulphate proteoglycan nationallicence eGFP : Enhanced green fluorescence protein nationallicence FTTM : Fourier transform traction microscopy nationallicence GDNF : Glial-derived neurotrophic factor nationallicence GFAP : Glial fibrillary acidic protein nationallicence HRP : Horseradish peroxidase nationallicence MAIs : Myelin-derived molecules nationallicence NgR : Nogo receptor nationallicence OEC : Olfactory ensheathing cell nationallicence OMgp : Oligodendrocyte-myelin glycoprotein nationallicence SCI : Spinal cord injury nationallicence TFM : Traction force microscopy nationallicence TUJ-1 : β3-Tubulin nationallicence Reginensi Diego Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Carulla Patricia Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Nocentini Sara Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Seira Oscar Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Serra-Picamal Xavier Integrative cell and tissue dynamics, Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain aut Torres-Espín Abel Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Edif. M, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain aut Matamoros-Angles Andreu Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Gavín Rosalina Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Moreno-Flores María Centro de Biología Molecular ‘Severo Ochoa', Universidad Autónoma de Madrid (CBM-UAM), Madrid, Spain aut Wandosell Francisco Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), CBM-UAM, Madrid, Spain aut Samitier Josep Nanobioengineering Laboratory, . Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain aut Trepat Xavier University of Barcelona, 08028, Barcelona, Spain aut Navarro Xavier Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Edif. M, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain aut del Río José Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut Cellular and Molecular Life Sciences Springer Basel 72/14(2015-07-01), 2719-2737 1420-682X 72:14<2719 2015 72 18 https://doi.org/10.1007/s00018-015-1869-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1869-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Reginensi Diego Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Carulla Patricia Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Nocentini Sara Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Seira Oscar Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Serra-Picamal Xavier Integrative cell and tissue dynamics, Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Torres-Espín Abel Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Edif. M, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain aut NATIONALLICENCE 700 1- Matamoros-Angles Andreu Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Gavín Rosalina Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Moreno-Flores María Centro de Biología Molecular ‘Severo Ochoa', Universidad Autónoma de Madrid (CBM-UAM), Madrid, Spain aut NATIONALLICENCE 700 1- Wandosell Francisco Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), CBM-UAM, Madrid, Spain aut NATIONALLICENCE 700 1- Samitier Josep Nanobioengineering Laboratory, . Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Trepat Xavier University of Barcelona, 08028, Barcelona, Spain aut NATIONALLICENCE 700 1- Navarro Xavier Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Edif. M, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain aut NATIONALLICENCE 700 1- del Río José Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/14(2015-07-01), 2719-2737 1420-682X 72:14<2719 2015 72 18