Olfactory Ecto-Mesenchymal Stem Cells in Laryngeal Nerve Regeneration in Rats

Abstract

Selective intralaryngeal reinnervation has been shown to be effective in experimental models. This consists of independently reinnerving the adductor and abductor of laryngeal muscles of the larynx, in order to prevent any misalignment of the axonal regrowth, improve the functional recovery and tend toward reduction of synkinesis. The surgical technique remains complex. Current research focuses on simplifying and improving this technique. Olfactory ectomesenchymal stem cells (OEMSC) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa. Recent reports suggest a neuroregenerative potential in various animal models of central and peripheral nervous systems injuries. The aim of this study was dual: to develop a simple surgical model of selective reinnervation applicable in humans and to evaluate the relevance of OEMSC-based cell therapy for improving axonal guidance. Eight Fisher syngeneic rats were used to carry out the OEMSCs culture. Thirty-four Fisher syngeneic rats were operated on, divided into three groups depending on the transplanting. For all the rats, we have performed a side to end anastomosis of the vagal nerve with the inferior laryngeal nerve by interposition of a nerve graft from the left femoral nerve. Then, the first group didn't have any injection, the second group has an injection of thrombin and the third group has an injection of one million EOMSCs. Three months after surgery, laryngeal muscle activity was evaluated by videolaryngoscopy and electromyography recordings. In order to illustrate the quality of axonal regrowth, a fluorescent tracer was injected into the right posterior crico-arytenoid muscle (PCA) to reveal the cellular bodies of the motoneurons responsible for reinnervation of the PCA in the central nervous system. In our study, no improvement was found during the videolaryngological functional evaluation or with regard to the electrical activity of the PCA muscle. The cells colabelled in retrograde tracing were numerous in all groups, reflecting abnormal axonal regeneration. The interposition of a nerve graft, as side to end anastomosis between the vagus nerve and the inferior laryngeal nerve, filled with OEMSCs, does not provide better reinnervation of a hemilarynx.

Keywords: Axonal regrowth; Larynx; Olfactory ectomesenchymal stem cells; Selective laryngeal reinnervation.