2024-03-29T02:28:15Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1393552021-05-24T09:24:58Zcom_10261_79com_10261_1col_10261_332
Reginensi, Diego
Wandosell, Francisco
Río, José Antonio del
Moreno-Flores, María Teresa
2016-10-26T08:28:56Z
2016-10-26T08:28:56Z
2015
Cellular and Molecular Life Sciences 72: 2719- 2737 (2015)
http://hdl.handle.net/10261/139355
10.1007/s00018-015-1869-3
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100008054
http://dx.doi.org/10.13039/501100008737
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.
eng
openAccess
Cell migration
Chondroitin sulphate proteoglycans
Traction force microscopy
Olfactory ensheathing cells
Nogo receptor ectodomain
Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord
artículo