Autologous myoblasts attenuate atrophy and improve tongue force in a denervated tongue model: a pilot study

Laryngoscope. 2014 Feb;124(2):E20-6. doi: 10.1002/lary.24352. Epub 2013 Oct 1.

Abstract

Objectives/hypothesis: Autologous muscle-derived stem cell (MdSC) therapy is a promising treatment to restore function. No group has evaluated MdSC therapy in a denervated tongue model. The purpose of this pilot investigation was to determine the extent of autologous MdSC survival, effects on tongue muscle atrophy, maximal contractile force, and lingual pressure in a denervated ovine tongue model.

Study design: Pilot animal experiment.

Methods: Bilateral implantable cuff electrodes were placed around the hypoglossal nerves in two Dorper cross ewes. Tensometer and high-resolution manometry (HRM) testing were performed during supermaximum hypoglossal nerve stimulation to assess baseline tongue strength. Sternocleidomastoid muscle biopsies were acquired to create autologous MdSC cultures. At 1 month, 5 × 10(8) green fluorescent protein (GFP)-labeled autologous MdSCs were injected into the partially denervated tongue. Two-months postinjection, lingual tensometer testing, HRM, and postmortem histological assessment were performed.

Results: GFP+ myofibers were identified in denervated tongue specimens indicating MdSC survival. Muscle fiber diameter was larger in GFP+ fibers for both tongue specimens, suggesting attenuation of muscle atrophy. Myofiber diameter was larger in GFP+ myofibers than preinjury diameters, providing evidence of new muscle formation. These myogenic changes led to a 27% increase in maximal tongue contractile force and a 54% increase in maximum base of tongue pressure in one animal.

Conclusions: Autologous MdSC therapy may be a viable treatment for the partially denervated tongue, with current findings demonstrating that injected MdSCs survived and fused with tongue myofibers, with a resultant increase in myofiber diameter and an increase in tongue strength.

Level of evidence: N/A.

Keywords: Stem cells; autologous; denervated tongue; dysphagia; muscle-derived stem cells; myoblast; myofibers; oropharyngeal dysphagia; satellite cells; tongue; tongue paralysis.

MeSH terms

  • Animals
  • Atrophy / prevention & control
  • Female
  • Models, Animal
  • Muscle Contraction
  • Muscle Denervation
  • Muscle Strength
  • Myoblasts / transplantation*
  • Pilot Projects
  • Sheep
  • Stem Cell Transplantation*
  • Tongue / innervation*
  • Tongue / pathology*
  • Transplantation, Autologous