Abstract

Olfactory ensheathing cells (OECs) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa (OM-OECs) or olfactory bulbs (OB-OECs). Recent reports suggest that, depending on their origin, OECs display different functional properties. We show here the complementary and additive effects of co-transplanting OM-OECs and OB-OECs after lesion of a peripheral nerve. For this, a selective motor denervation of the laryngeal muscles was performed by a section/anastomosis of the recurrent laryngeal nerve (RLN). Two months after surgery, recovery of the laryngeal movements and synkinesis phenonema were analyzed by videolaryngoscopy. To complete these assessments, measure of latency and potential duration were determined by electrophysiological recordings and myelinated nerve fiber profiles were defined based on toluidine blue staining. To explain some of the mechanisms involved, tracking of GFP positive OECs was performed. It appears that transplantation of OM-OECs or OB-OECs displayed opposite abilities to improve functional recovery. Indeed, OM-OECs increased recuperation of laryngeal muscles activities without appropriate functional recovery. In contrast, OB-OECs induced some functional recovery by enhancing axonal regrowth. Importantly, co-transplantation of OM-OECs and OB-OECs supported a major functional recovery, with reduction of synkinesis phenomena. This study is the first which clearly demonstrates the complementary and additive properties of OECs obtained from olfactory mucosa and olfactory bulb to improve functional recovery after transplantation in a nerve lesion model.

Highlights

  • Olfactory ensheathing cells (OECs) are specialized glial cells that guide the regeneration of non-myelinated olfactory axons from the peripheral nasal epithelium through the cribriform plate of the ethmoid bone and into the olfactory bulb (OB) [1,2]

  • We demonstrated in a vagus nerve (VN) lesion model, that both type of OECs could improve electrical muscular activity and nervous conduction, but that OM-OECs induce aberrant movements, whereas OB-OECs increase functional recovery [9]

  • The reinnervated-OM+OB treated group showed a significant augmentation of the angular movement of the vocal cords (10.9563.50u) (0.01,p,0.001) and a very significant improvement of the dynamic score (p,0.001) in comparison to the reinnervated control group

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Summary

Introduction

Olfactory ensheathing cells (OECs) are specialized glial cells that guide the regeneration of non-myelinated olfactory axons from the peripheral nasal epithelium through the cribriform plate of the ethmoid bone and into the olfactory bulb (OB) [1,2]. The source of OECs dramatically influences the success of cellular transplantation. It seems that OECs from OB and OM are specialized in different physiological processes [6,7,8], and have a different behavior after transplantation in vivo [7]. We demonstrated in a vagus nerve (VN) lesion model, that both type of OECs could improve electrical muscular activity and nervous conduction, but that OM-OECs induce aberrant movements, whereas OB-OECs increase functional recovery [9]. It appears too, that OM-OECs enhance tissue healing and reduce fibrosis. These two specific abilities could be crucial to improve recovery after lesion of the nervous system

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