TY - JOUR
T1 - Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord
AU - Reginensi, Diego
AU - Carulla, Patricia
AU - Nocentini, Sara
AU - Seira, Oscar
AU - Serra-Picamal, Xavier
AU - Torres-Espín, Abel
AU - Matamoros-Angles, Andreu
AU - Gavín, Rosalina
AU - Moreno-Flores, María Teresa
AU - Wandosell, Francisco
AU - Samitier, Josep
AU - Trepat, Xavier
AU - Navarro, Xavier
AU - Del Río, José Antonio
PY - 2015/7/24
Y1 - 2015/7/24
N2 - © 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.
AB - © 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.
KW - Cell migration
KW - Chondroitin sulphate proteoglycans
KW - Nogo receptor ectodomain
KW - Olfactory ensheathing cells
KW - Traction force microscopy
U2 - 10.1007/s00018-015-1869-3
DO - 10.1007/s00018-015-1869-3
M3 - Article
SN - 1420-682X
VL - 72
SP - 2719
EP - 2737
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 14
ER -