Nasal OEC transplantation promotes respiratory recovery in a subchronic rat model of cervical spinal cord contusion

Engraftment of nasal olfactory ensheathing cells (OEC) is considered as a promising therapeutic strategy for spinal cord repair and one clinical trial has already been initiated. However, while the vast majority of fundamental studies were focused on the recovery of locomotor function, the efficiency of this cellular tool for repairing respiratory motor dysfunction, which affects more than half of paraplegic/tetraplegic patients, remains unknown. Using a rat model that mimics the mechanisms encountered after a cervical contusion that induces a persistent hemi-diaphragmatic paralysis, we assessed the therapeutic efficiency of a delayed transplantation (2 weeks post-contusion) of nasal OECs within the injured spinal cord. Functional recovery was quantified with respiratory behavior tests, diaphragmatic electromyography and neuro-electrophysiological recording of the phrenic motoneurons while axogenesis was evaluated using immunohistochemistry. We show that 3 months post-transplantation, nasal OECs improve i) breathing movements, ii) activities of the ipsilateral diaphragm and corresponding phrenic nerve, and iii) axonal sprouting in the injury site. We also demonstrate that this functional partial recovery is mediated by the restoration of ipsilateral supraspinal command. Our study brings further evidence that olfactory ensheathing cells could have clinical application especially in tetraplegic patients with impaired breathing movements. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

Research highlights►A cervical cord contusion rat model induces a permanent respiratory deficit. ►A delayed OEC transplantation within the injury promotes respiratory improvements. ►Improvement results from an increased tidal volume and not from frequency change. ►Phrenic and diaphragm activity were improved up to 50% of healthy side. ►The functional improvements were correlated to axonal sprouting in the injury site.