Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia

PLoS One. 2018 Dec 11;13(12):e0208938. doi: 10.1371/journal.pone.0208938. eCollection 2018.

Abstract

In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity / drug effects
  • Cell Polarity / genetics
  • Child
  • Culture Media, Conditioned / pharmacology*
  • Deglutition / drug effects
  • Deglutition / physiology
  • Deglutition Disorders / drug therapy*
  • Deglutition Disorders / physiopathology
  • Dental Pulp / cytology
  • Dental Pulp / drug effects
  • Dental Pulp / growth & development
  • Disease Models, Animal
  • Female
  • Humans
  • Laryngeal Nerves / drug effects
  • Laryngeal Nerves / growth & development*
  • Laryngeal Nerves / pathology
  • Macrophages / drug effects
  • Male
  • Nerve Regeneration / drug effects*
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / growth & development
  • Rats
  • Regeneration
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Tooth, Deciduous / cytology
  • Tooth, Deciduous / drug effects

Substances

  • Culture Media, Conditioned

Grants and funding

This work was supported by Grants-in Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, grant number 7116K20569 to KS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.